scholarly journals TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis—Updated 2019

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1419 ◽  
Author(s):  
Dewidar ◽  
Meyer ◽  
Dooley ◽  
Meindl-Beinker
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Stellate Cell ◽  
Reactive Oxygen Species Generation ◽  
Mesenchymal Transition ◽  
Therapeutic Benefits ◽  
Liver Fibrogenesis

Liver fibrosis is an advanced liver disease condition, which could progress to cirrhosis and hepatocellular carcinoma. To date, there is no direct approved antifibrotic therapy, and current treatment is mainly the removal of the causative factor. Transforming growth factor (TGF)-β is a master profibrogenic cytokine and a promising target to treat fibrosis. However, TGF-β has broad biological functions and its inhibition induces non-desirable side effects, which override therapeutic benefits. Therefore, understanding the pleiotropic effects of TGF-β and its upstream and downstream regulatory mechanisms will help to design better TGF-β based therapeutics. Here, we summarize recent discoveries and milestones on the TGF-β signaling pathway related to liver fibrosis and hepatic stellate cell (HSC) activation, emphasizing research of the last five years. This comprises impact of TGF-β on liver fibrogenesis related biological processes, such as senescence, metabolism, reactive oxygen species generation, epigenetics, circadian rhythm, epithelial mesenchymal transition, and endothelial-mesenchymal transition. We also describe the influence of the microenvironment on the response of HSC to TGF-β. Finally, we discuss new approaches to target the TGF-β pathway, name current clinical trials, and explain promises and drawbacks that deserve to be adequately addressed.

scholarly journals Induction of tropomyosin during hepatic stellate cell activation and the progression of liver fibrosis

2008 ◽  
Vol 3 (2) ◽  
pp. 378-383 ◽  
Author(s):  
Kohji Otogawa ◽  
Tomohiro Ogawa ◽  
Ryoko Shiga ◽  
Kazuo Ikeda ◽  
Norifumi Kawada
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Hepatic Stellate Cell Activation

scholarly journals Dominant-negative soluble PDGF-β receptor inhibits hepatic stellate cell activation and attenuates liver fibrosis

2004 ◽  
Vol 84 (6) ◽  
pp. 766-777 ◽  
Author(s):  
Erawan Borkham-Kamphorst ◽  
Jens Herrmann ◽  
Doris Stoll ◽  
Jens Treptau ◽  
Axel M Gressner ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Dominant Negative ◽  
Hepatic Stellate Cell Activation ◽  
Β Receptor

scholarly journals Identification of GDF15 as A Pro-Fibrotic Factor in Mouse Liver Fibrosis Progression

2021 ◽  
Author(s):  
Peng Qi ◽  
Ming-Ze Ma ◽  
Jing-Hua Kuai
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Liver Tissue ◽  
Cell Activation ◽  
Stellate Cell ◽  
Neutralizing Antibody ◽  
Stellate Cells ◽  
Fibrosis Progression

Abstract Aim:To elucidate the inhibitory role of growth differentiation factor 15 (GDF15) in liver fibrosis and its possible activation mechanism in hepatic stellate cells of mice.Methods:We generated a GDF15-neutralizing antibody that can inhibit TGF-β1-induced activation of the TGF-β/Smad2/3 pathway in LX-2 cells. All the mice in this study were induced by carbon tetrachloride and thioacetamide. In addition, primary hepatic stellate cells from mice were isolated from fresh livers using Nycodenz density gradient separation. The severity and extent of liver fibrosis in mice were evaluated by Sirius Red and Masson staining. The effect of GDF15 on the activation of the TGF-β pathway was detected using dual-luciferase reporter assays and Western blotting assays.Results:The expression of GDF15 in cirrhotic liver tissue was higher than that in normal liver tissue. Blocking GDF15 with a neutralizing antibody resulted in a delay in primary hepatic stellate cell activation and remission of liver fibrosis induced by carbon tetrachloride or thioacetamide. Meanwhile, TGF-β pathway activation was partly inhibited by a GDF15-neutralizing antibody in primary hepatic stellate cells. These results indicated that GDF15 plays an important role in regulating HSC activation and liver fibrosis progression.Conclusions:The inhibition of GDF15 attenuates chemical-inducible liver fibrosis and delays hepatic stellate cell activation, and this effect is probably mainly attributed to its regulatory role in TGF-β signalling.

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