Synergistic effects of Platelet-derived growth factor-BB and Transforming growth factor-β1 on profibrogenic activities in hepatic stellate cells

2008 ◽  
Vol 46 (01) ◽  
Author(s):  
O Scherner ◽  
SK Meurer ◽  
E Borkham-Kamphorst ◽  
S Sauer-Lehnen ◽  
WN Vreden ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Synergistic Effects ◽  
Stellate Cells ◽  
Transforming Growth Factor Β1 ◽  
Platelet Derived Growth Factor

Cellular crosstalk mediated by platelet-derived growth factor BB and transforming growth factor β during hepatic injury activates hepatic stellate cells

2018 ◽  
Vol 96 (8) ◽  
pp. 728-741 ◽  
Author(s):  
Sowmya Mekala ◽  
SubbaRao V. Tulimilli ◽  
Ramasatyaveni Geesala ◽  
Kanakaraju Manupati ◽  
Neha R. Dhoke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Platelet Derived Growth Factor ◽  
Hepatic Tissue

Apoptotic hepatocytes release factors that activate hepatic stellate cells (HSCs), thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride, or thioacetamide. Histology of hepatotoxicant-induced diseased hepatic tissue correlated with differential expression of fibrosis-related genes. A marked increase in co-staining of transforming growth factor β receptor type II (TGFRIIβ) – desmin or α-smooth muscle actin – platelet-derived growth factor receptor β (PDGFRβ), markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V – cytokeratin expressing hepatocytes. To understand the molecular mechanisms of disease pathology, in vitro experiments were designed using the conditioned medium (CM) of hepatotoxicant-treated HepG2 cells supplemented to HSCs. A significant increase in HSC proliferation, migration, and expression of fibrosis-related genes and protein was observed, thereby suggesting the characteristics of an activated phenotype. Treating HepG2 cells with hepatotoxicants resulted in a significant increase in mRNA expression of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ). CM supplemented to HSCs resulted in increased phosphorylation of PDGFRβ and TGFRIIβ along with its downstream effectors, extracellular signal-related kinase 1/2 and focal adhesion kinase. Neutralizing antibodies against PDGF-BB and TGFβ effectively perturbed the hepatotoxicant-treated HepG2 cell CM-induced activation of HSCs. This study suggests PDGF-BB and TGFβ as potential molecular targets for developing anti-fibrotic therapeutics.

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

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 The Role of Hepatic Stellate Cells and Transforming Growth Factor-β1 in Cystic Fibrosis Liver Disease

2002 ◽  
Vol 160 (5) ◽  
pp. 1705-1715 ◽  
Author(s):  
Peter J. Lewindon ◽  
Tamara N. Pereira ◽  
Anita C. Hoskins ◽  
Kim R. Bridle ◽  
Richard M. Williamson ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Liver Disease ◽  
Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β1
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