scholarly journals Acetaldehyde stimulates the activation of latent transforming growth factor-β1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells

2002 ◽  
Vol 368 (3) ◽  
pp. 683-693 ◽  
Author(s):  
Anping CHEN
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β1 ◽  
Collagen Gene ◽  
Type Ii ◽  
Underlying Mechanisms ◽  
Tgf Β1

Acetaldehyde, the major active metabolite of alcohol, induces the activation of hepatic stellate cells (HSC), leading to over-production of α1(I) collagen and ultimately causing hepatic fibrosis. The underlying mechanisms of this process remain largely unknown. Transforming growth factor-β1 (TGF-β1) is a potent inducer of α1(I) collagen production. Accumulating evidence has shown a potential role for TGF-β1 in alcohol-induced hepatic fibrogenesis. The aims of this study were to determine the effect of acetaldehyde on TGF-β signalling, to elucidate the underlying mechanisms as well as to evaluate its role in expression of α1(I) collagen gene in cultured HSC. It was hypothesized that acetaldehyde activated TGF-β signalling by inducing the expression of elements in the TGF-β signal transduction pathway, which might contribute to α1(I) collagen gene expression in cultured HSC. Initial results revealed that acetaldehyde activated TGF-β signalling in cultured HSC. Additional studies demonstrated that acetaldehyde stimulated the secretion and activation of latent TGF-β1, and induced the expression of the type II TGF-β receptor (Tβ-RII). Further experiments found cis- and trans-activating elements responsible for Tβ-RII gene expression induced by acetaldehyde. Activation of TGF-β signalling by acetaldehyde contributed to α1(I) collagen gene expression in cultured HSC. In summary, this report demonstrated that acetaldehyde stimulated TGF-β signalling by increasing the secretion and activation of latent TGF-β1 as well as by inducing the expression of Tβ-RII in cultured HSC. Results from this report provided a novel insight into mechanisms by which acetaldehyde stimulated the expression of α1(I) collagen in HSC and a better understanding of effects of alcohol (or acetaldehyde) on hepatic fibrogenesis.

Transforming growth factor-β1 downregulation of Smad1 gene expression in rat hepatic stellate cells

2003 ◽  
Vol 285 (3) ◽  
pp. G539-G546 ◽  
Author(s):  
Hong Shen ◽  
Guojiang Huang ◽  
Mohammed Hadi ◽  
Patrick Choy ◽  
Manna Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Transforming Growth Factor Β1 ◽  
Dependent Manner ◽  
Tgf Β1

Smads are intracellular signaling molecules of the transforming growth factor-β (TGF-β) superfamily that play an important role in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat HSCs to investigate the expression and regulation of the Smad1 gene, which is a bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the expression and phosphorylation of Smad1 are increased during the activation of HSCs. Moreover, TGF-β significantly inhibits Smad1 gene expression in HSCs in a time- and dose-dependent manner. Furthermore, although both TGF-β1 and BMP2 stimulate the activation of HSCs, they have different effects on HSC proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of HSCs and TGF-β1 significantly inhibits the expression of the Smad1 gene.

scholarly journals Down-regulation of Human Type II Collagen Gene Expression by Transforming Growth Factor-β1 (TGF-β1) in Articular Chondrocytes Involves SP3/SP1 Ratio

2002 ◽  
Vol 277 (46) ◽  
pp. 43903-43917 ◽  
Author(s):  
Christos Chadjichristos ◽  
Chafik Ghayor ◽  
Jean-François Herrouin ◽  
Leena Ala-Kokko ◽  
Gunthram Suske ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Transforming Growth Factor Β1 ◽  
Collagen Gene ◽  
Type Ii ◽  
Human Type ◽  
Tgf Β1

scholarly journals Tanshinone IIA alters the transforming growth factor-β1/Smads pathway in angiotensin II-treated rat hepatic stellate cells

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092635
Author(s):  
Guo-wei Wei ◽  
Ke-yue Li ◽  
Ke-li Tang ◽  
Cheng-Xian Shi
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Protein Expression ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β1 ◽  
Tanshinone Iia ◽  
Mrna And Protein Expression ◽  
Tgf Β1

Objective To investigate the effects of tanshinone IIA on the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in angiotensin II-treated hepatic stellate cells (HSCs). Methods HSCs were cultured and treated with angiotensin II (10 μM) or angiotensin II (10 μM) plus tanshinone IIA (3, 10, or 30 μM). Cells were incubated for 48 hours and proliferation was determined with the Cell Counting Kit-8. The relative mRNA expression of TGF-β1, Smad4, and Smad7 was measured by quantitative real-time PCR, and the relative protein expression levels were investigated by western blotting. Results After angiotensin II treatment, cell proliferation was significantly accelerated. Furthermore, both the mRNA and protein expression of TGF-β1 and Smad4 was significantly up-regulated, while the mRNA and protein expression of Smad7 was significantly down-regulated compared with the control cells. Tanshinone IIA inhibited the observed effects of angiotensin II in a concentration-dependent manner, with significant inhibition exerted by tanshinone IIA at 10 and 30 μM. Conclusions Angiotensin II promotes the proliferation of HSCs, possibly by regulating the expression of components along the TGF-β1/Smads signaling pathway. Tanshinone IIA inhibits the angiotensin II-induced activation of this pathway, and may, therefore, have preventive and therapeutic effects in liver fibrosis.

scholarly journals Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

Molecules ◽  
2014 ◽  
Vol 19 (12) ◽  
pp. 19845-19867 ◽  
Author(s):  
Yannan Qin ◽  
Yaogang Zhong ◽  
Ganglong Yang ◽  
Tianran Ma ◽  
Liyuan Jia ◽  
...  
Keyword(s):  
Growth Factor ◽  
Concanavalin A ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β1

Prostaglandin E2 inhibits transforming growth factor β1-mediated induction of collagen α1(I) in hepatic stellate cells

2004 ◽  
Vol 41 (2) ◽  
pp. 251-258 ◽  
Author(s):  
Alex Y. Hui ◽  
Andrew J. Dannenberg ◽  
Joseph J.Y. Sung ◽  
Kotha Subbaramaiah ◽  
Baoheng Du ◽  
...  
Keyword(s):  
Growth Factor ◽  
Prostaglandin E2 ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β1

Curcumin suppresses the expression of extracellular matrix genes in activated hepatic stellate cells by inhibiting gene expression of connective tissue growth factor

2006 ◽  
Vol 290 (5) ◽  
pp. G883-G893 ◽  
Author(s):  
Shizhong Zheng ◽  
Anping Chen
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Growth Factor ◽  
Connective Tissue ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Tissue Growth ◽  
Collagen Gene ◽  
Ppar Γ ◽  
Collagen Gene Expression

Upon liver injury, quiescent hepatic stellate cells (HSCs), the most relevant cell type for hepatic fibrogenesis, become active and overproduce extracellular matrix (ECM). Connective tissue growth factor (CTGF) promotes ECM production. Overexpression of CTGF during hepatic fibrogenesis is induced by transforming growth factor (TGF)-β. We recently demonstrated that curcumin reduced cell growth and inhibited ECM gene expression in activated HSCs. Curcumin induced gene expression of peroxisome proliferator-activated receptor (PPAR)-γ and stimulated its activity in activated HSCs, which was required for curcumin to suppress ECM gene expression, including αI(I)-collagen. The underlying mechanisms remain largely unknown. The aim of this study was to elucidate the mechanisms by which curcumin suppresses αI(I)-collagen gene expression in activated HSCs. We hypothesize that inhibition of αI(I)-collagen gene expression in HSCs by curcumin is mediated by suppressing CTGF gene expression through attenuating oxidative stress and interrupting TGF-β signaling. The present report demonstrated that curcumin significantly reduced the abundance of CTGF in passaged HSCs and suppressed its gene expression. Exogenous CTGF dose dependently abrogated the inhibitory effect of curcumin. Activation of PPAR-γ by curcumin resulted in the interruption of TGF-β signaling by suppressing gene expression of TGF-β receptors, leading to inhibition of CTGF gene expression. The phytochemical showed its potent antioxidant property by significantly increasing the level of total glutathione (GSH) and the ratio of GSH to GSSG in activated HSCs. De novo synthesis of cellular GSH was a prerequisite for curcumin to interrupt TGF-β signaling and inhibited gene expression of CTGF and αI(I)-collagen in activated HSCs. Taken together, our results demonstrate that inhibition of αI(I)-collagen gene expression by curcumin in activated HSCs results from suppression of CTGF gene expression through increasing cellular GSH contents and interruption of TGF-β signaling. These results provide novel insights into the mechanisms underlying inhibition of HSC activation by curcumin.

scholarly journals Fibroblast Growth Factor-1 Suppresses TGF-β-Mediated Myofibroblastic Differentiation of Rat Hepatic Stellate Cells

2016 ◽  
Vol 59 (4) ◽  
pp. 124-132
Author(s):  
Eva Peterová ◽  
Lucie Podmolíková ◽  
Martina Řezáčová ◽  
Alena Mrkvicová
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Collagen Gel ◽  
Stellate Cells ◽  
Critical Event ◽  
Fibroblast Growth ◽  
Enhanced Production ◽  
Tgf Β1

Myofibroblast expansion is a critical event in the pathogenesis of liver fibrosis. The activation of hepatic stellate cells (HSC) to myofibroblast (MFB) results in the enhanced production of extracellular matrix (ECM). In this study, we explored the effect of acidic fibroblast growth factor (FGF-1) treatment on a transforming growth factor (TGF-β1) induced MFB conversion. We used HSC-T6 cell line, which represents well-established model of activated HSC. These cells strongly expressed α-smooth muscle actin (α-SMA) and fibronectin (FN-EDA) after stimulation with TGF-β1, which is a stimulus for MFB differentiation and ECM production. FGF-1 reduced proteins expression to levels comparable with untreated cells. Mild repression of secreted gelatinases was seen in culture media after FGF-1 treatment. The exposure of cells to collagen gel leads to changes in cell morphology and in expression of MFB markers. Lack of α-SMA in cells embedded to collagen gel was detected. When stimulated with TGF-β1, the cells increased expression of FN-EDA, but not α-SMA. Although the cells on plastic and in collagen gel show different properties, FGF-1 reduced expression of FN-EDA in both conditions. Disrupting TGF-β1 signalling pathway represents a potential strategy for the treatment of fibrosis. We showed that FGF-1 could antagonize signals initiated by TGF-β1.

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