| 27259994 | Chromatin immunoprecipitation quantitative PCR confirmed that acetylated LKB1 interacts with and activates TGFbeta1 promoter, which is inhibited by SIRT1 |
| 27259994 | Knocking down either SIRT1 or HERC2 results in an increased association of LKB1 with the positive regulatory elements of TGFbeta1 promoter |
| 27358050 | LATS-YAP/TAZ controls lineage specification by regulating TGFbeta signaling and Hnf4alpha expression during liver development |
| 27358050 | It increases BEC and fibroblast proliferation by up-regulating TGFbeta signalling, but suppresses hepatoblast to hepatocyte differentiation by repressing Hnf4alpha expression |
| 27114850 | Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-kappaB, and TGF-beta pathways, can also induce the expression of HIF-1alpha protein to facilitate cell survival in normoxia |
| 27067789 | Using the HPMC and GCC adherence and invasion assay, we demonstrated that transforming growth factor beta 1 (TGF-beta)1-induced HPMC senescence was attenuated by silencing the Endoglin expression, which also prevented GCC attachment and invasion |
| 27067789 | Up-regulated Endoglin expression induced HPMC senescence via TGF-beta1 pathway |
| 26474459 | Moreover, macrophages induced fibroblasts migration, differentiation and secretion of collagen, which were inhibited in the presence of TGF-beta receptor inhibitors |
| 26474459 | Finally, we show that the macrophage-dependent induction of PAR-1 driven TGF-beta activation was mediated by FXa |
| 26433963 | The search for mediators of senescent HPMC activity using specific neutralizing antibodies and recombinant exogenous proteins showed that the intensified angiogenic potential of cancer cells was elicited by IL-6 and TGF-beta1 |
| 26414019 | We tested the hypothesis that areca nut alkaloids induce senescence in oral fibroblasts and promote the secretion of invasion-promoting transforming growth factor beta (TGF-beta) and matrix metalloproteinase-2 (MMP-2) |
| 26414019 | TGF-beta and MMP-2 levels were measured using ELISA |
| 26414019 | Treated cells also showed a three- fivefold increase in TGF-beta and a small non-significant increase in MMP-2 |
| 26414019 | CONCLUSIONS: Areca nut alkaloids induce senescence in oral fibroblasts and promote increased secretion of TGF-beta and perhaps MMP-2 that may create a tissue environment thought to be critical in the progression of OSMF to malignancy |
| 26391655 | In vivo, defective VSMC autophagy led to upregulation of MMP9, TGFB and CXCL12 and promoted postinjury neointima formation and diet-induced atherogenesis |
| 26284488 | The search for mediators of senescent HPMC activity showed that increased SW480 cell proliferation was stimulated by IL-6, migration by CXCL8 and CCL2, invasion by IL-6, MMP-3 and uPA, and epithelial-mesenchymal transition by TGF-beta1 |
| 26257076 | However, STIM1 also promoted cell migration and the epithelial-to-mesenchymal transition by activating TGF-beta, Snail and Wnt/beta-Catenin pathways |
| 26187313 | Transforming growth factor-beta (TGF-beta) has both tumor suppressive and oncogenic activities |
| 26187313 | Autocrine TGF-beta signaling supports tumor survival and growth in certain types of cancer, and the TGF-beta signaling pathway is a potential therapeutic target for these types of cancer |
| 26187313 | TGF-beta induces p21 expression, and p21 is considered as an oncogene as well as a tumor suppressor, due to its anti-apoptotic activity |
| 26187313 | Thus, we hypothesized that autocrine TGF-beta signaling maintains the expression of p21 at levels that can support cell growth |
| 26187313 | To verify this hypothesis, we sought to examine p21 expression and cell growth in various cancer cells following the inhibition of autocrine TGF-beta signaling using siRNAs targeting TGF-beta signaling components and SB431542, a TGF-beta receptor inhibitor |
| 26187313 | Results from the present study show that p21 expression and cell growth were reduced by knockdown of TGF-beta signaling components using siRNA in MDA-MB231 and A549 cells |
| 26187313 | These data suggest that autocrine TGF-beta signaling is required to sustain p21 levels for positive regulation of cell cycle |
| 26187313 | The TGF-beta signaling pathway was not associated with the SB431542-mediated induction of p21 expression |
| 26078812 | Transforming growth factor-beta (TGF-beta) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease |
| 26078812 | In this review we are analyzing the interplay between TGF-beta and ROS in tumorigenesis and cancer progression |
| 26078812 | TGF-beta can control ROS production directly or by downregulating antioxidative systems |
| 26078812 | Meanwhile, ROS can influence TGF-beta signaling and increase its expression as well as its activation from the latent complex |
| 26078812 | In addition, both TGF-beta and ROS are able to induce cell senescence, which in one way protects damaged cells from neoplastic transformation but also may collaborate in cancer progression |
| 26078812 | The mutual collaboration of TGF-beta and ROS in tumorigenesis is highly complex, and, due to their differential roles in tumor progression, careful consideration should be taken when thinking of combinatorial targeting in cancer therapies |
| 25982278 | IFNgamma induces oxidative stress, DNA damage and tumor cell senescence via TGFbeta/SMAD signaling-dependent induction of Nox4 and suppression of ANT2 |
| 25982278 | The expression of Nox4/Nox1 required Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling and the effect was mediated by downstream activation of transforming growth factor-beta (TGFbeta) secretion and consequent autocrine/paracrine activation of the TGFbeta/Smad pathway |
| 25982278 | In contrast to mouse B16 cells, inability of TC-1 cells to respond to IFNgamma/TNFalpha by DDR and senescence correlated with the lack of TGFbeta and Nox4 response, supporting the role of ROS induced by NADPH oxidases in cytokine-induced senescence |
| 25982278 | Overall, our data reveal differences between cytokine effects in mouse and human cells, and mechanistically implicate the TGFbeta/SMAD pathway, via induction of NADPH oxidases and suppression of ANT2, as key mediators of IFNgamma/TNFalpha-evoked genotoxicity and cellular senescence |
| 25792544 | In addition, the expression of cellular senescence features, such as the progressive rise in the enzymatic senescence-associated b-galactosidase (SA-b-gal) activity, IL6, IL1b, and TGFb expression, was observed throughout pituitary tumor development |
| 25693643 | We further showed that the lack of cell-cell interactions during epidermal commitment led to heightened production of TGF-beta1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system |
| 25683165 | Here we report that the upregulation of SIRT6 expression was required for transforming growth factor (TGF)-beta1 and H2O2/HOCl reactive oxygen species (ROS) to promote the tumorigenicity of hepatocellular carcinoma (HCC) cells |
| 25647436 | Balding DPCs secreted higher levels of the negative hair growth regulators transforming growth factor beta 1 and 2 in response to H2O2 but not cell culture-associated oxidative stress |
| 25279424 | Members of the TGF-beta superfamily, TGF-beta1, TGF-beta3, and BMP9, are key propagators of both inhibition and initiation of angiogenesis |
| 25220407 | Etoposide-induced formation of these complexes and repression of ANT2 were relatively late events co-incident with production and secretion of, and dependent on, TGF-beta |
| 25134354 | Particular attention was paid to the role of telomeres, the activity of senescence effectors at the level of the cell cycle, and the action of oxidative stress and transforming growth factor beta1 |
| 25015975 | CSE exposure stimulated TGF-beta1 production, and both inhibition of TGF-beta receptor kinase and TGF-beta1 siRNA blocked CSE modulation of fibroblast function |
| 24985060 | Growth factors, such as Transforming Growth Factor-beta (TGF-beta), possess the ability to impede cancer development in the early stages, via alterations in either apoptosis, cell proliferation, or the promotion of cellular senescence |
| 24985060 | However, later in the pathogenesis, advanced prostate cancer cells become insensitive to the previously beneficial effects of TGF-beta |
| 24925089 | Moreover, JMJD3 can activate TGF-beta signaling through the SMAD3 pathway |
| 24917460 | Transforming growth factor beta1 (TGF-beta1) induces Mv1Lu cell senescence through inactivating glycogen synthase kinase 3 (GSK3), thereby inactivating complex IV and increasing intracellular ROS |
| 24917460 | When Mv1Lu cells were exposed to TGF-beta1, PKCdelta phosphorylation simultaneously increased with GSK3 phosphorylation, and then AKT and ERK were phosphorylated |
| 24792119 | Transcriptome analysis indicated reduced TGF-beta signaling and perturbation of genes involved in HSC proliferation and differentiation |
| 24495866 | Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting |
| 24495866 | BACKGROUND: Transforming growth factor beta (TGF-beta1) is a pleiotropic cytokine, which is deregulated in atherosclerosis; however the role of age in this process is unknown |
| 24495866 | We aimed to assess whether TGF-beta1 signaling is affected by age |
| 24495866 | Levels of TGF-beta1 were measured by ELISA in sera from 169 patients undergoing coronary artery bypass grafting (CABG) |
| 24495866 | In VSMC from these patients undergoing abdominal surgery, secretion of TGF-beta1 was determined by ELISA of cell-conditioned media |
| 24495866 | RESULTS: In VSMC from aged patients we observed a lower TGF-beta1 secretion, measured as TGF-beta1 concentration in cell conditioned medium (p<0 |
| 24495866 | In a similar manner, there was an age-dependent decrease of serum TGF-beta1 levels in CABG patients (p=0 |
| 24495866 | CONCLUSIONS: VSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-beta1 secretion and signaling |
| 24383372 | TGF-beta1 is upregulated in stenotic valves and induces calcification and collagen synthesis in cultured valve interstitial cells |
| 24383372 | It has been shown previously that TGF-beta1 increases reactive oxygen species (ROS) in these cells in association with calcifying nodule formation, but the cellular signaling pathways responsible for these TGF-beta1-induced effects are not well defined |
| 24383372 | METHODS: Cultured porcine aortic valve interstitial cells were used to investigate the effects of inhibitors of TGF-beta1 signaling pathways on 3H-proline incorporation into the extracellular matrix, the peak number of calcifying nodules formed, redox stress as dichlorofluorescein diacetate (DCF-DA) fluorescence, and senescence-associated beta-galactosidase staining |
| 24269635 | In cultured chondrocytes, IL-1beta and TNF-alpha suppressed FOXO1, while TGF-beta and PDGF increased FOXO1 and FOXO3 expression |
| 24147049 | TGF-beta1 does not induce senescence of multipotent mesenchymal stromal cells and has similar effects in early and late passages |
| 24147049 | Transforming growth factor-beta 1 (TGF-beta1) stimulates a broad range of effects which are cell type dependent, and it has been suggested to induce cellular senescence |
| 24147049 | On the other hand, long-term culture of multipotent mesenchymal stromal cells (MSCs) has a major impact on their cellular physiology and therefore it is well conceivable that the molecular events triggered by TGF-beta1 differ considerably in cells of early and late passages |
| 24147049 | In this study, we analyzed the effect of TGF-beta1 on and during replicative senescence of MSCs |
| 24147049 | Stimulation with TGF-beta1 enhanced proliferation, induced a network like growth pattern and impaired adipogenic and osteogenic differentiation |
| 24147049 | TGF-beta1 did not induce premature senescence |
| 24147049 | Nonetheless, relative gene expression differences provoked by TGF-beta1 at individual time points or in a time course dependent manner (stimulation for 0, 1, 4 and 12 h) were very similar in MSCs of early and late passage |
| 24147049 | These results support the notion that TGF-beta1 has major impact on MSC function, but it does not induce senescence and has similar molecular effects during culture expansion |
| 23871936 | Bystander senescence in human peritoneal mesothelium and fibroblasts is related to thrombospondin-1-dependent activation of transforming growth factor-beta1 |
| 23871585 | DNA damage was prevented by treatment with a TGF-beta1 inhibitor (P < 0 |
| 23871585 | The phenotype is recapitulated by subjecting human pluripotent stem cells to hypoxia during cardiac differentiation and rescued by inhibition of TGF-beta1 |
| 23770676 | Amongst them, TGF-beta ligands play a major role by regulating p15(INK4b) and p21(CIP1) |
| 23688930 | MicroRNAs (miRs), a class of molecules involved in gene expression regulation, are emerging as modulators of some pathways, including NF-kappaB, mTOR, sirtuins, TGF-beta and Wnt, that may be related to inflammation, cellular senescence and age-related diseases, cancer included |
| 23468063 | Following pretreatment with subcytotoxic concentrations of copper sulfate, U87-MG tumor cells showed typical aging characteristics, including reduced cell proliferation, cell enlargement, increased level of senescence-associated beta-galactosidase (SA beta-gal) activity, and overexpression of several senescence-associated genes, p16, p21, transforming growth factor beta-1 (TGF-beta1), insulin growth factor binding protein 3 (IGFBP3) and apolipoprotein J (ApoJ) |
| 23415666 | Special attention is paid to the causes of the very fast dynamics of HPMC senescence, and in particular to the role of non-telomeric DNA damage, the autocrine activity of TGF-beta1, and the causative effects of oxidative stress |
| 23385065 | Persistent cytokine signaling and activated DDR evoke senescence in normal bystander cells, accompanied by activation of the JAK/STAT, TGFbeta/SMAD and IL1/NFkappaB signaling pathways |
| 23385065 | Whereas inhibition of IL6/STAT signaling had no effect on DDR induction in bystander cells, inhibition of either TGFbeta/SMAD or IL1/NFkappaB pathway resulted in decreased ROS production and reduced DDR in bystander cells |
| 23374245 | Cells were compared in terms of proliferation, DNA damage, time course and extent of myogenic marker expression during differentiation, fusion, size of the formed myotubes, secretion of the myogenic regulatory cytokine TGF-beta1 and sensitivity to TGF-beta1 treatment |
| 23374245 | The senescent cells exhibited a greater number of cells with DNA damage (gamma-H2AX positive), showed impaired expression of markers of differentiation, fused less well, formed smaller myotubes and secreted more TGF-beta |
| 23358854 | Progression of genotype-specific oral cancer leads to senescence of cancer-associated fibroblasts and is mediated by oxidative stress and TGF-beta |
| 23358854 | Keratinocytes from GU-OSCC produced high levels of reactive oxygen species (ROS) and this was associated with an increase in the production of transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 in stromal fibroblasts |
| 23358854 | The data demonstrate that malignant keratinocytes from GU-OSCC, but not their pre-malignant counterparts, produce high levels of ROS, which, in turn, increase TGF-beta1 expression and induce fibroblast activation and senescence in a p5-independent manner |
| 23272236 | To confirm selectivity of the SASP-RAP response, cells were treated with senescence-related and -unrelated stimuli (IL-1beta, LPS, TNF-alpha and TGF-beta), and induction of senescence markers and activity of SASP-RAP were evaluated in parallel |
| 23224139 | In the CPC-P, genes related to early stages of developmental processes, nervous system development and neurogenesis, skeletal development, bone and cartilage development were downregulated, while those involved in mesenchymal cell differentiation and heart development were upregulated, together with the transcriptional activation of TGFbeta/BMP signaling pathway |
| 24678443 | In particular, modulations in Wnt, TGFbeta, Notch and FGF emanating from aged skeletal muscle fibers or the systemic milieu have emerged as age-related alterations that significantly impact both the maintenance of the satellite cell pool and skeletal muscle regenerative efficacy |
| 22904099 | Compared with young EC, senescent cells displayed increased expression of senescence-associated beta-galactosidase, nitric oxide synthase (eNOS), and AKT kinase, and secreted increased amounts of growth factors (VEGF, TGF-beta), cytokines (IL-6, IL-8, MCP-1), adhesion molecules (sICAM-1), and matrix proteins (fibronectin) |
| 22889746 | Indoxyl sulfate, a uremic toxin, induces renal fibrosis through expression of transforming growth factor-beta(1) (TGF-beta(1)) in proximal tubular cells |
| 22889746 | Stat3 small interfering RNA suppressed indoxyl sulfate-induced expression of an inflammation marker gene (monocyte chemotactic protein-1), fibrosis marker genes (TGF-beta(1), alpha-smooth muscle actin) and a subunit of nuclear factor-kB (p65), and attenuated a cellular senescence marker, senescence-associated beta-galactosidase activity |
| 22820504 | Knockdown of p16(INK4A) expression reversed the senescent features of MSCs and upregulated TGF-beta expression |
| 22802912 | The fibrotic response is associated with altered expression of growth factors and cytokines, including increased levels of transforming growth factor-beta1 (TGF-beta1) and the more recent observation that increased levels of several insulin-like growth factor binding proteins (IGFBPs) are associated with a number of fibrotic conditions |
| 22652454 | Transforming growth factor beta1 (TGF beta1) induces Mv1Lu cell senescence by persistently producing mitochondrial reactive oxygen species (ROS) through decreased complex IV activity |
| 22652454 | Here, we investigated the molecular mechanism underlying the effect of TGF beta1 on mitochondrial complex IV activity |
| 22652454 | TGF beta1 progressively phosphorylated the negative regulatory sites of both glycogen synthase kinase 3 (GSK3) alpha and beta, corresponding well to the intracellular ROS generation profile |
| 22652454 | Finally, TGF beta1 treatment decreased the binding of the subunit 6b to GSK3 and subunit 6b phosphorylation |
| 22514746 | Premature senescence and increased TGFbeta signaling in the absence of Tgif1 |
| 22514746 | Transforming growth factor beta (TGFbeta) signaling regulates cell cycle progression in several cell types, primarily by inducing a G1 cell cycle arrest |
| 22514746 | Additionally, we show that Tgif1 null MEFs are more sensitive to TGFbeta-mediated growth inhibition, and that treatment with a TGFbeta receptor kinase inhibitor increases proliferation of Tgif1 null MEFs |
| 22514746 | Conversely, persistent treatment of wild type cells with low levels of TGFbeta slows proliferation and induces senescence, suggesting that TGFbeta signaling also contributes to cellular senescence |
| 22514746 | We suggest that in the absence of Tgif1, a persistent increase in TGFbeta responsive transcription and a reduced ability to deal with hyperoxic stress result in premature senescence in primary MEFs |
| 22494436 | In chronic wounds, a variety of changes in receptors have been identified: decreased integrin alpha5beta1 receptors affect the integration of fibronectin and subsequent keratinocyte migration; integrin alphavbeta6 stimulate transforming growth factor (TGF)-beta and may increase the susceptibility to ulceration and fibrosis; however, TGF-beta signal receptors have been found to be dysfunctional in many chronic wounds; additionally receptor interactions result in increased senescent cells including fibroblasts, myofibroblasts and even keratinocytes - this produces a degradative ECM and wound bed and corrosive chronic wound fluid |
| 22385081 | Both the oral epithelium and the mesenchyme have elevated levels of TGF-beta(1) in OSMF in vivo |
| 22385081 | However, in cultured fibroblasts, secreted levels of TGF-beta(1,) other cytokines and the matrix metalloproteinases 1 and 2 showed no association with OSMF |
| 22200425 | Indoxyl sulfate stimulates progression of CKD by increasing renal expression of profibrotic cytokines such as transforming growth factor beta 1 |
| 22175510 | Identification of a specific factor that plays a causative role in stem cell dysfunction in aging is consistent with data showing that transforming growth factor-beta (TGF-beta) inhibits satellite cell-mediated repair |
| 22095030 | Nevertheless, regulation of other pathways which are not relevant to p53, yet important for tumorigenesis such as TGF-beta and NF-kappaB, by ING proteins is also observed |
| 22037217 | Loss of TGF-beta signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation |
| 22037217 | However, Pten-deficient mice developed full-penetrance HNSCC in combination with type I TGF-beta receptor (Tgfbr1) deletion |
| 22019769 | In particular, we discuss how Myc-evoked apoptosis serves as a signal for macrophage attraction and activation, followed by the secretion of TGF-beta as a cytokine that is capable of terminally arresting Myc-driven lymphoma cells without causing further DNA damage and without launching a senescence-associated, pro-inflammatory, and, therefore, potentially detrimental cytokine response in the target population |
| 21985896 | 5 population doublings) human aortic endothelial cells demonstrated greater smooth muscle (spindle) morphological changes, expression of SMalphaA and collagen I, nuclear factor-kappaB activation, and transforming growth factor-beta (TGF-beta) (all p < 0 |
| 21985896 | Based on increases in SMalphaA, stimulation with the proinflammatory cytokine tumor necrosis factor-alpha, but not with TGF-beta, induced EnMT in early passage cells similar to that observed in late passage cells |
| 21832251 | Inhibitors of NF-kappaB (pyrrolidine dithiocarbamate and isohelenin) and NF-kappaB p65 small interfering RNA (siRNA) suppressed indoxyl sulfate-induced senescence-associated beta-galactosidase activity and expression of p53, transforming growth factor (TGF)-beta1, and alpha-smoothe muscle actin (SMA) |
| 21224216 | We found that TGF-beta induced senescence in primary HBEC by increasing p21 expression, and, whereas TGF-beta also induced SIRT6, it was not sufficient to inhibit cellular senescence |
| 21037952 | Cell-autonomous and cell-dependent mechanisms have both been implicated, and recent results suggest a critical role for autocrine factors, including thrombospondin-1 and TGF-beta |
| 20818171 | Other gene products like p53, SUV39H1 or TGFbeta promoted senescence, which together with apoptosis contributed to tumor suppression |
| 20627123 | Dynamic SUMO regulation controls the biological outcomes initiated by various growth factors involved in cartilage homeostasis, including basic fibroblast growth factors (bFGF or FGF-2), transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1) |
| 20533544 | The effect of WNT/beta-catenin on nucleus pulposus (NP) cells was examined by transfection experiments, an MTT assay, senescence-associated beta-galactosidase staining, a cell cycle analysis, and a transforming growth factor (TGFbeta)/bone morphogenetic protein (BMP) pathway-focused microarray analysis |
| 20533544 | We also demonstrated that WNT/beta-catenin signaling induced the expression of matrix metalloproteinases (MMPs) and TGFbeta in NP cells |
| 20533544 | CONCLUSION: The activation of WNT/beta-catenin signaling promotes cellular senescence and may modulate MMP and TGFbeta signaling in NP cells |
| 20227040 | Tumor stroma-derived TGF-beta limits myc-driven lymphomagenesis via Suv39h1-dependent senescence |
| 20227040 | Using the Emu-myc transgenic mouse lymphoma model, we show here in vivo that apoptotic lymphoma cells activate macrophages to secrete transforming growth factor beta (TGF-beta) as a critical non-cell-autonomous inducer of cellular senescence |
| 20227040 | Accordingly, neutralization of TGF-beta action, like genetic inactivation of the senescence-related histone methyltransferase Suv39h1, significantly accelerates Myc-driven tumor development via cancellation of cellular senescence |
| 20016203 | Senescence and decreased NO production were observed in cells and several signaling pathways - such as IFN/STAT, IGF, TGF-beta, cytoskeleton rearrangement and lipid metabolism - were altered at P4, as judged from the microarray analysis |
| 21994573 | Finally, antiproliferative and apoptosis deficiencies involving TGF-beta, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation |
| 19766114 | Here we found that TGF-beta1 enforced G(1) cell cycle arrest and cellular senescence in human U-937 myeloid tumor cells ectopically expressing v-Myc, which contains a stabilizing mutation frequently found in lymphomas |
| 19651821 | One of these, transforming growth factor beta (TGF-beta), and nitric oxide (NO) were found to elevate numbers of gamma-H2AX/53BP1 foci in normal cell cultures similar to levels found in bystander cells, and this elevation was abrogated by NO synthase inhibitors, TGF-beta blocking antibody and antioxidants |
| 19171648 | Subtoxic oxidative stress induces senescence in retinal pigment epithelial cells via TGF-beta release |
| 19171648 | The effects of TGF-beta blocking on the oxidative stress-induced expression of senescence-associated biomarkers were investigated by simultaneous incubation with neutralizing antibodies against the TGF-beta1, -beta2, and -beta3 isoforms and the TGF-betaII receptor |
| 19171648 | Treatment with TGF-beta1 and -beta2 showed similar changes |
| 19171648 | H(2)O(2)and TGF-beta1 and -beta2 markedly enhanced the expression of p21 but downregulated pRb |
| 19171648 | Simultaneous treatment with neutralizing antibodies against the TGF-beta1, -beta2, and -beta3 isoforms and the TGF-betaII receptor prevented the oxidative stress-mediated elevation of senescence-associated biomarkers |
| 19171648 | CONCLUSIONS: Oxidative stress, TGF-beta1, and TGF-beta2 are capable of inducing cellular senescence in cultured human RPE cells |
| 19171648 | Therefore, reduction of oxidative stress and minimizing TGF-beta may help to prevent senescence-associated changes in the RPE as seen in early age-related macular degeneration |
| 19122829 | RESULTS: Fetal bovine serum and TGFbeta1 activated the transdifferentiation of corneal stromal cells into fibroblasts and myofibroblasts, indicated by cell spreading, renewed assembly of actin filaments and enhanced expression of extracellular matrix components, all of which were suppressed by the addition of HDAC inhibitors |
| 19099650 | Morphology, senescence-associated beta-galactosidase (SA-beta-gal) staining and cell cycle analysis were used to evaluate the changes in BMMSCs at cellular level while real-time RT-PCR was used to detect the alterations in senescence related gene expression including p16INK4a, p21Cip1/Waf1, p53 and TGF-beta1 |
| 18974388 | Here, we have analyzed the expression, during EC senescence, of 2 different isoforms (L, long; S, short) of endoglin, an auxiliary transforming growth factor (TGF)-beta receptor involved in vascular remodeling and angiogenesis |
| 18974388 | Next, the effect of S-endoglin protein on the TGF-beta receptor complex was studied |
| 18974388 | Transgenic mice overexpressing S-endoglin in ECs showed hypertension, decreased hypertensive response to NO inhibition, decreased vasodilatory response to TGF-beta(1) administration, and decreased endothelial nitric oxide synthase expression in lungs and kidneys, supporting the involvement of S-endoglin in the NO-dependent vascular homeostasis |
| 18676497 | IGFBP5 has also been shown to induce similar effects to TGFB1, but, in addition, it is strongly implicated in the process of senescence which is now believed to be a significant factor in these diseases |
| 18498775 | This effect could be partly reduced by neutralizing TGF-beta1 activity |
| 18498775 | The timely treatment with N-tert-butyl-alpha-phenylnitrone (PBN) reduced oxidative stress, the number of early senescent cells, TGF-beta1 secretion, and ultimately extended the population life span |
| 18206261 | TGF-beta1 and IL-4 downregulate human papillomavirus-16 oncogene expression but have differential effects on the malignant phenotype of cervical carcinoma cells |
| 18206261 | Results indicated that downregulation of E6 and E7 levels by IL-4 in CaSki cells is weaker than that exerted by TGF-beta1, a known LCR inhibitor, although both cytokines are equally active in suppressing LCR-driven transcriptional activity in a reporter cell line |
| 18206261 | Moreover, only TGF-beta rescued p53 expression, Rb response pathway, and induced cellular senescence |
| 17662305 | Synergistic activation of extracellular signal-regulated kinase in human dermal fibroblasts by human telomerase reverse transcriptase and transforming growth factor-beta1 |
| 17662305 | Toward this end, we treated hTERT-transfected human dermal fibroblasts (HDFs) with transforming growth factor (TGF)-beta1 and investigated the activation of extracellular signal-regulated kinase (ERK) 1/2, vital mediators of cell proliferation |
| 17662305 | MATERIALS AND METHODS: Primary HDFs were transfected with either recombinant adenovirus expressing hTERT (Ad-hTERT) or control adenovirus (Ad-NULL) and subsequently treated with TGF-beta1 (2 pg/mL) |
| 17662305 | TGF-beta1, TGFbeta-RI, TGFbeta-RII, and Col1 A1 mRNA levels were analyzed by real-time PCR |
| 17662305 | The synergistic ERK 1/2 activation in Ad-hTERT-transfected HDFs occurred as early as 10 min and was sustained for at least 30 min after TGF-beta1 treatment |
| 17662305 | There were no statistically significant differences in TGF-beta1, TGFbeta-RI, TGFbeta-RII, and Col1 A1 mRNA levels between HDFs that were transfected with Ad-hTERT and those that were transfected with Ad-NULL after TGF-beta1 treatment |
| 17575140 | Transforming growth factor beta (TGFbeta) has been implicated as a candidate cytokine to mediate this communication |
| 17575140 | When their TGFbeta signaling was blocked, the fibroblasts and stromal cells still stimulated tumor initiation but no longer supported tumor growth as control cells did |
| 17575140 | The loss of the tumor growth-promoting activity of the stromal cells with attenuated TGFbeta signaling was not associated with altered cellular senescence or tumor angiogenicity |
| 17575140 | TGFbeta and the medium conditioned by the prostate carcinoma cells stimulated myofibroblast differentiation of the intact stromal cells, but not the stromal cells with attenuated TGFbeta signaling |
| 17575140 | Gene microarray and quantitative reverse transcription-PCR analyses showed that TGFbeta up-regulated a host of genes in stromal cells that are involved in tissue remodeling and wound healing |
| 17575140 | Thus, our study provides evidence for TGFbeta as a supporting agent in tumor progression through the induction of a perpetual wound healing process in the tumor microenvironment |
| 17532297 | In this study, we investigated whether cellular senescence was involved in the stimulation of hMSCs growth by FGF-2 and the expression levels of transforming growth factor-beta1 and -beta2 (TGF-betas) |
| 17473528 | We focused on the relationship between the hMSC proliferation and their transforming growth factor beta (TGFbeta) signaling during in vitro culture |
| 17473528 | The mRNA expressions of TGFbeta1, TGFbeta2, and TGFbeta receptor type I (TGFbetaRI) in hMSCs increased with the length of cell culture |
| 17325661 | We have previously reported that transforming growth factor beta (TGF-beta) represses the expression of the hTERT gene |
| 17297436 | Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-beta1 |
| 17297436 | Late-passage HPMC exposed to HG displayed marked hypertrophy and released increased amounts of fibronectin and TGF-beta1 |
| 17297436 | Exposure of early-passage HPMC to exogenous recombinant TGF-beta1 induced a senescence marker SA-beta-Gal in a dose-dependent manner and mimicked other senescence-associated alterations induced by HG |
| 17291987 | This effect was associated with reduced levels of SA-beta-Gal and 8-OH-dG, diminished TGF-beta1 and fibronectin release, and less pronounced hypertrophy of aged HPMC |
| 16883569 | Elongated giant mitochondria were also observed in TGF beta1- or H2O2-induced senescent Mv1Lu cells and in old human diploid fibroblasts (HDFs) |
| 16717406 | First, we screened for an extrinsic signal that can induce cellular senescence in human lung adenocarcinoma cell line A549, and identified transforming growth factor-beta (TGF-beta) as the cellular senescence-inducing factor |
| 16717406 | Cancer cells senesced by treatment with TGF-beta impaired tumorigenicity both in vitro and in vivo, suggesting that cellular senescence functions as a tumor suppression mechanism |
| 16686600 | Id-1 modulates senescence and TGF-beta1 sensitivity in prostate epithelial cells |
| 16686600 | BACKGROUND INFORMATION: Loss of sensitivity to TGF-beta1 (transforming growth factor beta1)-induced growth arrest is an important step towards malignant transformation in human epithelial cells, and Id-1 (inhibitor of differentiation or DNA binding-1) has been associated with cell proliferation and cell-cycle progression |
| 16686600 | Here, we investigated the role of Id-1 in cellular sensitivity to TGF-beta1 |
| 16283872 | Another important conclusion of this study is that blockade of transforming growth factor-beta1 had a pronounced "rescue effect" in the aged, preventing entrance of HDFs into cellular senescence |
| 23598653 | Genetic and transgenic analyses have identified several conserved signaling pathways that function in the ovary to regulate stem cell maintenance, division and differentiation, including the wingless, hedgehog, JAK/STAT, insulin and TGF-beta pathways |
| 16123802 | Deregulated TGF-beta signaling in leukemogenesis |
| 16123802 | The transforming growth factor-beta (TGF-beta) pathway plays an important role in cellular homeostasis by regulating cell growth inhibition, cellular senescence, differentiation and apoptosis |
| 16123802 | Deregulated TGF-beta signaling is known to be involved in a variety of human cancers, including those of the colon, pancreas, breast and prostate |
| 16123802 | While TGF-beta is a potent negative regulator of hematopoiesis, the role of aberrant TGF-beta signaling in leukemogenesis remains largely unknown |
| 16123802 | Recently, evidence demonstrating deregulated TGF-beta signaling in leukemogenesis, particularly in acute promyelocytic leukemia (APL), has started to emerge |
| 16123802 | In this review, we summarize the current progress towards the understanding of the molecular mechanisms by which aberrant TGF-beta signaling may participate in leukemogenesis |
| 15734488 | In this study, we hypothesized that neonatal fibroblasts (NNF) cultured under elevated pressure will demonstrate premature aging and that this effect will be augmented by an inflammatory mediator, transforming growth factor beta (TGF-beta) |
| 15734488 | Some pressure-exposed NNF were also cultured with TGF- beta (1 ng/ml) |
| 15734488 | NNF grown with TGF-beta did not show augmented SA-beta-Gal staining |
| 15734488 | TGF-beta did not augment the aging effect |
| 15659039 | Cultured pressure ulcer fibroblasts show replicative senescence with elevated production of plasmin, plasminogen activator inhibitor-1, and transforming growth factor-beta1 |
| 15659039 | Also, senescent ulcer bed fibroblasts produced higher levels of transforming growth factor-beta1, but these were not significantly different from senescent normal skin fibroblasts |
| 15659039 | Although senescent ulcer fibroblasts produce elevated levels of plasminogen activator inhibitor-1 and transforming growth factor-beta1, the ratio of these factors to plasmin levels suggests that this may have little influence on extracellular matrix synthesis or maintenance in the chronic wound |
| 15610763 | Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation |
| 15610763 | It has been assumed that TGF-beta1 plays a key role in the aging prostate by inducing premature senescence and favoring myofibroblast differentiation |
| 15610763 | Therefore, we evaluated the stromal cell phenotypes of human primary adult prostatic fibroblasts (n=3) and the molecular and cellular mechanisms of growth arrest after treatment with TGF-beta1 and of in vitro cellular senescence |
| 15610763 | TGF-beta1 induced neither expression of senescence-associated markers nor genes involved in terminal growth arrest, such as senescence-associated beta-galactosidase and cyclin-dependent kinase (cdk) inhibitors p16(Ink4A) and p21(Cip1) but increased p15(Ink4B) protein expression |
| 15610763 | Genes specifically up-regulated by transdifferentiation but not by cellular senescence of PrSCs were metalloproteinase 1 tissue inhibitor (Timp1), transgelin (Tagln), gamma 2 actin (Actg2), plasminogen activator inhibitor 1 (Serpinel), insulin-like growth factor binding protein 3 (Igfbp3), parathyroid hormone-like hormone (Pthlp), Tgfb-1, four and a half LIM domains 2 (Fhl-2), hydrogen peroxide-inducible clone 5 (Hic5) and cartilage oligomeric matrix protein (Comp) |
| 15610763 | Other genes, such as Cdc28 protein kinase 1 (Cks1b), v-myb myeloblastosis viral oncogene homolog (MybL2), pyruvate kinase, muscle 2 (Pkm2) and Forkhead box M1 (FoxM1), were down-regulated only upon TGF-beta1 treatment but not by cellular senescence |
| 15580303 | Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-beta1 expression |
| 15580303 | TGF-beta1 expression from the whey acidic protein promoter (WAP) in triply transgenic females did not prevent the appearance of PI-MEC after pregnancy despite the absence of full lactation or their ability to proliferate and produce progeny with diverse cellular fates in situ upon subsequent pregnancies |
| 15356634 | Cytoplasmic PML function in TGF-beta signalling |
| 15356634 | Transforming growth factor beta (TGF-beta) is a pluripotent cytokine that controls key tumour suppressive functions, but cancer cells are often unresponsive to it |
| 15356634 | Here we show that cytoplasmic Pml is an essential modulator of TGF-beta signalling |
| 15356634 | These cells also have impaired phosphorylation and nuclear translocation of the TGF-beta signalling proteins Smad2 and Smad3, as well as impaired induction of TGF-beta target genes |
| 15356634 | Expression of cytoplasmic Pml is induced by TGF-beta |
| 15356634 | Furthermore, cytoplasmic PML physically interacts with Smad2/3 and SARA (Smad anchor for receptor activation) and is required for association of Smad2/3 with SARA and for the accumulation of SARA and TGF-beta receptor in the early endosome |
| 15356634 | The PML-RARalpha oncoprotein of APL can antagonize cytoplasmic PML function and APL cells have defects in TGF-beta signalling similar to those observed in Pml-null cells |
| 15356634 | Our findings identify cytoplasmic PML as a critical TGF-beta regulator, and further implicate deregulated TGF-beta signalling in cancer pathogenesis |
| 15158681 | Rapid senescence was induced into human lung adenocarcinoma A549 cells by transforming growth factor-beta1 |
| 15147944 | We postulate that CTGF expression is controlled, in part, by transforming growth factor-beta (TGF-beta), in view of the high levels of TGF-beta isoforms as well as type I and II receptors detected only in late PDL of HDF cells |
| 15147944 | To verify this hypothesis, we stimulated early PDL cells with TGF-beta1 as well as stress inducing agents such as hydrogen peroxide |
| 14580871 | TGF-beta cytokines increase senescence-associated beta-galactosidase activity in human prostate basal cells by supporting differentiation processes, but not cellular senescence |
| 14580871 | Basal cell cultures established from prostate explants (n=3) were either grown into cellular senescence, or stimulated with TGF-beta1, beta2 and beta3 |
| 14580871 | Similar to cellular senescence, TGF-beta stimulation resulted in an increase of SA-beta galactosidase (SA-beta-gal) activity, flattened and enlarged cell morphology, and down-regulation of the inhibitor of differentiation Id-1 |
| 12959928 | Transforming growth factor (TGF)-beta has been shown to induce senescence in A549 lung cancer cells, and both TGF-beta and bone morphogenetic protein (BMP) 2 can suppress the transformed phenotype of A549 cells in vitro |
| 12784623 | We have previously reported that transforming growth factor beta (TGF-beta) triggers two independent senescence programs, 1) replicative senescence dependent upon telomere shortening and 2) premature senescence independent of telomere shortening, in the cell line of A549 human lung adenocarcinoma |
| 12784623 | We used A549 cells treated with TGF-beta for a long time (over 50 days), where senescence was induced in a telomere-shortening-dependent or an independent way |
| 12764277 | Altered proliferative responses of dermal fibroblasts to TGF-beta1 may contribute to chronic venous stasis ulcer |
| 12764277 | 5, 5, 10, and 20 ng/mL of transforming growth factor-beta(1) (TGF-beta(1)) demonstrated maximal cell proliferation at 5 ng/mL of TGF-beta(1) on day 4 |
| 12764277 | Under these conditions, CVI dermal fibroblasts were challenged with and without TGF-beta(1) and evaluated for proliferative responses on plates coated with polystyrene, collagen, and fibronectin |
| 12764277 | The diminished proliferation observed in class 4 LC cells was reversible with TGF-beta(1) stimulation (P < |
| 12734568 | An example using TGFb1 treatment of OC cells to examine signaling and target gene activation is presented |
| 12593448 | Supplementation of TGF-beta to growth media induced marked suppression of proliferation to target cells along with morphologic and phenotypic features of terminal differntiation or senescence |
| 12593448 | This suggest that HMEC cells on subsequent passages undergo some genetic and phenotypic alterations resulting in production of growth inhibitory factor like TGF-beta which induces cessation of their proliferation alone with features of senescence |
| 11402321 | In a study of FVB/N mice with the transgene, WAP-TGFbeta1, we discovered that mammary epithelial stem cells were prematurely aged due to ectopic expression of TGF-beta1 |
| 11402321 | Only one mammary tumor appeared in 17 TGF-beta1 females while 15 were collected from 29 wild type sisters |
| 11402321 | Although the number of positive takes was significantly reduced with TGF-beta1 cells, both MMTV-infected TGF-beta1 and wild type cells produced hyperplastic outgrowths suggesting that premalignant transformation was achieved in each group |
| 11344338 | Specific responses to transforming growth factor beta (TGF-beta) were also analyzed |
| 11344338 | Exposure of the MK/T-1 cells to TGF-beta induces the expression of smooth muscle alpha-actin (ASMA), the activation of MAP Kinase (p38-MAPK) and morphological changes consistent with cytoskeletal reorganization |
| 11060295 | Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts |
| 11060295 | In this work, we show that transforming growth factor-beta1 (TGF-beta1) regulates the induction of several of these biomarkers in SIPS: cellular morphology, senescence-associated beta-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein J, osteonectin, and SM22 mRNA |
| 11060295 | Indeed, the neutralization of TGF-beta1 or its receptor (TGF-beta RII) using specific antibodies decreases sharply the percentage of cells positive for the senescent-associated beta-galactosidase activity and displaying a senescent morphology |
| 11060295 | Results obtained on fibroblasts retrovirally transfected with the human papillomavirus E7 cDNA suggest that retinoblastoma protein (Rb) regulates the expression of TGF-beta1 in stressful conditions, leading to SIPS and overexpression of these four genes |
| 10906512 | Overexpression of mRNAs of TGFbeta-1 and related genes in fibroblasts of Werner syndrome patients |
| 10906512 | Among the six up-regulated mRNAs were three mRNAs that coded TGFbeta-1 and two proteins, their expressions of which were increased by TGFbeta-1 |
| 10906512 | These results together with the fact that TGFbeta-1 up-regulates the expression of ECM proteins strongly suggest that TGFbeta-1 has a key role in accelerated cellular senescence of fibroblasts of WS patients |
| 10767578 | Because studies support the involvement of ECM components, TGF-beta and p53 in tumor suppressing mechanisms, our data supports the hypothesis that cellular senescence and upregulation of ECM proteins may be associated with tumor preventive functions |
| 10082664 | Here we demonstrate that TGF-beta induces a morphological change and expression of senescence-associated beta-galactosidase activity in the human lung adenocarcinoma cell line A549 cells within a week after the addition |
| 10082664 | These TGF-beta induced phenotypic changes are thought to characterize the rapid onset of senescence |
| 10082664 | When A549 cells were treated with TGF-beta, cell growth was not completely arrested, but the activity of telomerase was down regulated via transcriptional repression of telomerase reverse transcriptase, which led to a shortening of the telomere during long-term culture and finally resulted in replicative senescence |
| 10082664 | These results indicate that TGF-beta is able to induce a rapid senescence in A549 cells without significantly inhibiting cell growth and can further direct A549 cells to a replicative senescence state via the suppression of telomerase which culminates in telomere shortening |
| 10082664 | All these experimental results suggest that TGF-beta transmits several separate and independent signals to shift A549 cells back to a normal senescent cell |
| 9079631 | Its mRNA level is induced by transforming growth factor beta-1 and indomethacin and inhibited by phorbol ester and retinoic acid |
| 8912720 | Endogenous TGF-beta activity is modified during cellular aging: effects on metalloproteinase and TIMP-1 expression |
| 8912720 | The cytokine TGF-beta1 is known to regulate the expression of each of these three genes and to be synthesized and secreted by cultured human fibroblasts |
| 8912720 | This suggested the hypothesis that the age-specific modulation of collagenase, stromelysin, and TIMP-1 expression is the result of a change in TGF-beta1 activity during replicative senescence |
| 8912720 | To test this hypothesis, the responses of early, mid, and late passage (presenescent) fibroblast cell cultures to a TGF-beta neutralizing antibody were evaluated |
| 8912720 | In early passage cell cultures, exposure to TGF-beta neutralizing antibody resulted in a significant increase in the expression of collagenase and stromelysin and decreased TIMP-1 expression |
| 8912720 | The antibody did not affect expression of either of those genes by late passage cell cultures, although late passage cultures did respond to added TGF-beta1 |
| 8912720 | Quantification of the levels of active TGF-beta, using a growth inhibition assay, indicates that the level of active TGF-beta1 is decreased during replicative senescence, supporting the conclusion that the modulation of collagenase, stromelysin, and TIMP-1 expression results from diminished TGF-beta activity |
| 7929412 | Characterization of the TGF beta 1-inducible hic-5 gene that encodes a putative novel zinc finger protein and its possible involvement in cellular senescence |
| 7929412 | Transforming growth factor (TGF) beta 1 is a potent cytokine that inhibits the growth of several types of cells |
| 7929412 | Our earlier study suggested that the mouse osteoblastic cell line, MC3T3-E1, was sensitive to growth inhibition by TGF beta 1 and that this effect was partly mediated by H2O2 |
| 7929412 | To identify the molecules that participate in the negative regulation of growth by these stimuli, we carried out differential screening of cDNA libraries and isolated a set of genes induced by TGF beta 1 |
| 7929412 | Among the clones isolated, one originally named tsc-5 was found to be induced by H2O2 as well as TGF beta 1 |
| 7929412 | Although the relationship between hic-5 function and the signal transduction pathway of TGF beta 1 remains unresolved, these results implied that hic-5 has some role in the growth-inhibitory pathway associated with in vitro senescence, and that down-regulation of hic-5 contributes to tumorigenesis |
| 8504493 | Autocrine production of TGF-alpha and TGF-beta during tumour progression of rat oral keratinocytes |
| 8504493 | This study describes a new technique to separate transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta (TGF-beta) from culture supernatants using ion exchange chromatography; assays of competitive inhibition of ligand binding were used to quantify the amount of growth factor |
| 8504493 | The autocrine production of TGF-alpha and TGF-beta was examined in oral keratinocyte cell lines derived from the palatal and lingual mucosa of rats painted with the carcinogen 4-nitroquinoline N-oxide (4NQO) |
| 8504493 | The autocrine production of TGF-beta was variable with the majority of cell lines producing markedly little TGF-beta; three cell lines (R4T, R8BP, R9T) produced more TGF-beta than normals |
| 8504493 | The production of TGF-beta was unrelated to tumour progression, the expression of TGF-beta cell surface receptors or TGF-alpha production |
| 8504493 | The results indicate that the autocrine production of TGF-alpha and TGF-beta are not accurate markers of tumour progression in the rat 4NQO model of oral carcinogenesis |
| 1716619 | Epidermal growth factor and its receptor, basic fibroblast growth factor, transforming growth factor beta-1, and interleukin-1 alpha messenger RNA production in human corneal endothelial cells |
| 1716619 | The authors tried to determine whether human corneal endothelial cells in primary culture synthesize messenger RNA (mRNA) coding for epidermal growth factor (EGF), EGF receptor, basic fibroblast growth factor (FGFb), transforming growth factor beta-1 (TGFb1), and interleukin-1 alpha (IL-1 alpha) |
| 1716619 | The polymerase chain reaction (PCR) was used to amplify the growth factors (EGF, FGFb, TGFb1, and IL-1 alpha), EGF receptor, and beta actin sequences from each of the cDNA samples |
| 1716619 | The EGF mRNAs were detected by PCR alone in four of the samples from proliferative cultures, TGFb1 mRNAs in three, and IL-1 alpha mRNAs in three |
| 1713586 | We demonstrate that serum deprivation; placement of cells into primary culture; and growth factors such as transforming growth factor beta 1, retinoic acid, and 1,25-dihydroxyvitamin D3 can all change the alternative splicing of fibronectin pre-mRNA in the ED-A, ED-B, and type III connecting sequence exons |
| 3494524 | TGF-beta inhibition of endothelial cell proliferation: alteration of EGF binding and EGF-induced growth-regulatory (competence) gene expression |
| 3494524 | Transforming growth factor-beta (TGF-beta) inhibits the growth of endothelial cells derived from various sources, including human umbilical vein, bovine aorta, and rat heart |
| 3494524 | Long-term exposure of rat heart endothelial cells to TGF-beta also induces dramatic changes in morphology that are characteristic of senescent cells |
| 3494524 | Additionally, the EGF-induced expression of specific competence genes (c-myc, JE, KC) is decreased, whereas the induction of c-fos gene expression by EGF is unaltered by TGF-beta treatment |
| 3494524 | These data suggest that growth inhibitors such as TGF-beta may act by altering the cell's response to growth-stimulatory factors |
