Silymarin suppresses hepatic stellate cell activation in a dietary rat model of non-alcoholic steatohepatitis: Analysis of isolated hepatic stellate cells

Hepatic stellate cells are liver-specific perivascular cells, identified as the major source of collagen in liver fibrosis, following their activation and conversion to myofibroblast-like cells.

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GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2014.10.001 ◽

2014 ◽

Vol 1842 (12) ◽

pp. 2367-2377 ◽

Cited By ~ 22

Author(s):

Qian Zhou ◽

Wei Guan ◽

Haowen Qiao ◽

Yuanyuan Cheng ◽

Ziqiang Li ◽

...

Keyword(s):

Hepatic Stellate Cell ◽

Hepatic Stellate Cells ◽

Cell Activation ◽

Stellate Cell ◽

Binding Protein ◽

Stellate Cells ◽

Hepatic Stellate Cell Activation

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

10.21203/rs.3.rs-296829/v1 ◽

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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Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.279.1.g7 ◽

2000 ◽

Vol 279 (1) ◽

pp. G7-G11 ◽

Cited By ~ 131

Author(s):

Francis J. Eng ◽

Scott L. Friedman

Keyword(s):

Hepatic Stellate Cell ◽

Cell Activation ◽

Stellate Cell ◽

Gene Array ◽

Stellate Cells ◽

Cellular Responses ◽

Autocrine Signaling ◽

Cellular Behavior ◽

Hepatic Stellate Cell Activation ◽

Complex Process

Hepatic stellate cell activation is a complex process. Paradoxes and controversies include the origin(s) of hepatic stellate cells, the regulation of membrane receptor signaling and transcription, and the fate of the cells once liver injury resolves. Major themes have emerged, including the dominance of autocrine signaling and the identification of counterregulatory stimuli that oppose key features of activated cells. Advances in analytical methods including proteomics and gene array, coupled with powerful bioinformatics, promise to revolutionize how we view cellular responses. Our understanding of stellate cell activation is likely to benefit from these advances, unearthing modes of regulating cellular behavior that are not even conceivable on the basis of current paradigms.

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