scholarly journals Long Non-Coding RNA (LncRNA)-ATB Promotes Inflammation, Cell Apoptosis and Senescence in Transforming Growth Factor-β1 (TGF-β1) Induced Human Kidney 2 (HK-2) Cells via TGFβ/SMAD2/3 Signaling Pathway

2020 ◽  
Vol 26 ◽  
Author(s):  
Han Sun ◽  
Cong Ke ◽  
Lin Zhang ◽  
Changjun Tian ◽  
Zhihui Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Human Kidney ◽  
Transforming Growth Factor Β1 ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Tgf Β1

scholarly journals Transforming growth factor-β1 impairs CFTR-mediated anion secretion across cultured porcine vas deferens epithelial monolayer via the p38 MAPK pathway

2013 ◽  
Vol 305 (8) ◽  
pp. C867-C876 ◽  
Author(s):  
Sheng Yi ◽  
Fernando Pierucci-Alves ◽  
Bruce D. Schultz
Keyword(s):  
Cystic Fibrosis ◽  
Growth Factor ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Vas Deferens ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Transforming Growth Factor Β1 ◽  
Anion Secretion ◽  
Tgf Β1

The goal of this study was to determine whether transforming growth factor-β1 (TGF-β1) affects epithelial cells lining the vas deferens, an organ that is universally affected in cystic fibrosis male patients. In PVD9902 cells, which are derived from porcine vas deferens epithelium, TGF-β1 exposure significantly reduced short-circuit current ( Isc) stimulated by forskolin or a cell membrane-permeant cAMP analog, 8-pCPT-cAMP, suggesting that TGF-β1 affects targets of the cAMP signaling pathway. Electrophysiological results indicated that TGF-β1 reduces the magnitude of current inhibited by cystic fibrosis transmembrane conductance regulator (CFTR) channel blockers. Real-time RT-PCR revealed that TGF-β1 downregulates the abundance of mRNA coding for CFTR, while biotinylation and Western blot showed that TGF-β1 reduces both total CFTR and apical cell surface CFTR abundance. These results suggest that TGF-β1 causes a reduction in CFTR expression, which limits CFTR-mediated anion secretion. TGF-β1-associated attenuation of anion secretion was abrogated by SB431542, a TGF-β1 receptor I inhibitor. Signaling pathway studies showed that the effect of TGF-β1 on Isc was reduced by SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK). TGF-β1 exposure also increased the amount of phospho-p38 MAPK substantially. In addition, anisomycin, a p38 MAPK activator, mimicked the effect of TGF-β1, which further suggests that TGF-β1 affects PVD9902 cells through a p38 MAPK pathway. These observations suggest that TGF-β1, via TGF-β1 receptor I and p38 MAPK signaling, reduces CFTR expression to impair CFTR-mediated anion secretion, which would likely compound the effects associated with mild CFTR mutations and ultimately would compromise male fertility.

Rho kinase mediates transforming growth factor-β1-induced vasculogenic mimicry formation: involvement of the epithelial–mesenchymal transition and cancer stemness activity

2020 ◽  
Vol 52 (4) ◽  
pp. 411-420 ◽  
Author(s):  
Xue Zhang ◽  
Jigang Zhang ◽  
Heming Zhou ◽  
Gaolin Liu ◽  
Qin Li
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Vasculogenic Mimicry ◽  
Rho Kinase ◽  
Transforming Growth Factor Β1 ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, has been identified in several malignant tumors, including hepatocellular carcinoma (HCC). Rho kinase (ROCK) plays an important role in various types of cancers. However, whether ROCK participates in transforming growth factor-β1 (TGF-β1)-induced VM formation is unclear. Here, we evaluated the role of ROCK in TGF-β1-induced VM formation in HCC. Our findings showed that the TGF-β1/ROCK signaling pathway is involved in VM formation by inducing the epithelial–mesenchymal transition. Furthermore, TGF-β1 and ROCK were found to play distinct roles in the cancer stem cell phenotype during VM formation. These results provide insights into potential antitumor therapies for inhibiting VM by targeting the TGF-β1/ROCK signaling pathway in HCC.

scholarly journals Requirement for Transforming Growth Factor β1 in Controlling T Cell Apoptosis

2001 ◽  
Vol 194 (4) ◽  
pp. 439-454 ◽  
Author(s):  
WanJun Chen ◽  
Wenwen Jin ◽  
Hongsheng Tian ◽  
Paula Sicurello ◽  
Mark Frank ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Growth Factor ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Death Receptor ◽  
Cell Receptor ◽  
Transforming Growth Factor Β1 ◽  
T Cell Apoptosis ◽  
Tgf Β1

Transforming growth factor (TGF)-β1, a potent immunoregulatory molecule, was found to control the life and death decisions of T lymphocytes. Both thymic and peripheral T cell apoptosis was increased in mice lacking TGF-β1 (TGF-β1−/−) compared with wild-type littermates. Engagement of the T cell receptor enhanced this aberrant T cell apoptosis, as did signaling through either the death receptor Fas or the tumor necrosis factor α receptor in peripheral T cells. Strikingly, TGF-β was localized within the mitochondria of normal T cells, and the absence of TGF-β1 resulted in disruption of mitochondrial membrane potential (Δψm), which marks the point of no return in a cell condemned to die. This TGF-β–dependent regulation of viability appears dissociable from the TGF-β1 membrane receptor–Smad3 signaling pathway, but associated with a mitochondrial antiapoptotic protein Bcl–XL. Thus, TGF-β1 may protect T cells at multiple sites in the death pathway, particularly by maintaining the essential integrity of mitochondria. These findings may have broad implications not only for T cell selection and death in immune responses and in the generation of tolerance, but also for defining the mechanisms of programmed cell death in general.

Transforming Growth Factor-β1 Inhibits the Maturation of Dendritic Cells Via Toll-Like Receptor 4 Signaling Pathway.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3861-3861
Author(s):  
Haibo Mou ◽  
Maofang Lin ◽  
He Huang
Keyword(s):  
Dendritic Cells ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
P38 Kinase ◽  
Toll Like Receptor 4 ◽  
Tgf Β1

Abstract We have demonstrated that transforming growth factor-β1(TGF-β1) inhibits the maturation of mouse bone marrow derived dendritic cells (DCs). TGF-β1 treated DCs (TGFβ-DCs) are resistant to maturation stimulus -lipopolysaccharide (LPS) and might have some correlation with the down-modulation of Toll-like receptor 4 (TLR4) expression. It was known TLR4 binds LPS from Gram-negative bacteria, triggering signaling pathways that lead to the activation of NF-κB, ERK1/2 and p38 MAPK and ensuing gene expression of proinflammatory factors. In the current study, we further estimated the activities of NF-κB, ERK1/2 and p38 proteins involved in TLR4 signaling pathway. Using EMSA method, we found the NF-κB DNA binding activity in immature DCs (imDCs) was significantly increased in response to LPS, but addition of TGF-β1 to DCs inhibited NF-κB binding. Moreover, TGF-β1 was effective in suppressing LPS-induced activation of ERK1/2 and p38 kinase, the level of phosphorylation of ERK1/2 and p38 kinase were lower than imDCs measured by Western Blot. After treatment of imDCs and TGFβ-DCs with LPS for 24 h, the production of IL-12p70 of TGFβ-DCs was significantly less than that of imDCs(115.4±15.2 pg/ml vs 517.0±29.7 pg/ml, P<0.01), but the level of Th2 cytokine-IL-10 was elevated(132.1±17.5 pg/ml vs 75.1±16.6 pg/ml, P<0.05), indicating that exposure to TGF-β1 impaired the capability of DCs to produce high amounts of bioactive IL-12p70. According to the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), the expressions of chemokines MIP-1α mRNA on TGFβ-DCs after LPS stimulation were lower than imDCs at each time point. The lower expressions of MCP-1 and IP-10 on TGFβ-DCs at irregular pattern after LPS treatment, whereas the expressions RANTES were no different. Hence, the results suggested TGF-β1 maybe directly inhibit TLR4 expression on DCs, and then interfere with the activity of downstream key proteins, such as NF-κB, ERK1/2 and p38. Ultimately, TGF-β1 treated DCs were resistance to LPS, down-regulated the expression of costimulatory molecular on DCs and decreased the secretion of inflammatory cytokines.

scholarly journals Human Papillomavirus Type 5 E6 Oncoprotein Represses the Transforming Growth Factor β Signaling Pathway by Binding to SMAD3

2006 ◽  
Vol 80 (24) ◽  
pp. 12420-12424 ◽  
Author(s):  
Jose-Andres Mendoza ◽  
Yves Jacob ◽  
Patricia Cassonnet ◽  
Michel Favre
Keyword(s):  
Human Papillomavirus ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Cellular Transformation ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
E6 Oncoprotein ◽  
E6 Protein ◽  
Tgf Β1

ABSTRACT Mechanisms of cellular transformation associated with human papillomavirus type 5 (HPV5), which is responsible for skin carcinomas in epidermodysplasia verruciformis (EV) patients, are poorly understood. Using a yeast two-hybrid screening and molecular and cellular biology experiments, we found that HPV5 oncoprotein E6 interacts with SMAD3, a key component in the transforming growth factor β1 (TGF-β1) signaling pathway. HPV5 E6 inhibits SMAD3 transactivation by destabilizing the SMAD3/SMAD4 complex and inducing the degradation of both proteins. Interestingly, the E6 protein of nononcogenic EV HPV9 failed to interact with SMAD3, suggesting that downregulation of the TGF-β1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.

Sign in / Sign up

Export Citation Format

Share Document