Sesha, J., Ho, V., George, J., and Hebbard, L. (2009) Adiponectin is an important regulator of hepatic stellate cell function. Journal of Gastroenterology and Hepatology, 24 (Suppl. 2). A274-A274.

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Abstract

The key transition in the remodelling of extracellular matrix during fibro- genesis is the transformation of the hepatic stellate cell (HSC) from a quiescent to an activated myofibroblast-like phenotype. Adiponectin (Ad), an adipocytokine with anti-inflammatory, anti-atherogenic and insulin sen- sitising properties induces an anti-fibrogenic HSC profile in vitro. Ad signals through AMP-activated protein kinase (AMPK) and can induce the anti-inflammatory cytokine IL-10. The aim of this study was to determine the signalling intermediaries of Ad’s anti-fibrogenic effects.

Methods: Activated primary rat HSCs were treated with Ad for either 4 or 24 hours. To determine the signalling pathways that mediate Ad’s action on HSCs, cells were transfected with IL-10 siRNA or treated with the AMPK antagonists, Compound C or AraA. HSC proliferation and apoptosis was assessed by BrdU incorporation and Caspase 3 activity, respectively. Collagen-1, TGF-b, CTGF, TIMP-1, IL-10 and Bcl-2 mRNA expression was determined by real-time quantitative PCR and normalised to Sp-1.

Results: Ad treatment for 4 hours decreased Bcl-2 expression 7-fold and increased the expression of IL-10 mRNA 25-fold (p < 0.05) in activated HSCs. IL-10 siRNA transfection diminished IL-10 expression by 90% and increased Bcl-2 levels 40-fold as compared to control. Similarly, on Ad treatment Caspase 3 activity was up-regulated 2-fold and reversed with transfection of IL-10 siRNA. IL-10 recombinant protein treatment resulted in a 15-fold decrease of Bcl-2 expression. Ad retarded TGF-b induced Collagen-1 and CTGF expression. Ad treatment for 24 hours reduced proliferation in HSCs by 50% and increased the expression of TIMP-1, while treatment with Compound C or AraA and Ad concurrently reduced TIMP-1 expression.

Conclusion: Adiponectin reduces HSC proliferation, abrogates Colla- gen-1 and CTGF expression, is apoptotic and induces IL-10 in activated HSCs. IL-10 recombinant protein reduces Bcl-2 expression. These data suggest that adiponectin’s anti-fibrogenic effects in HSCs, may in part be mediated by IL-10. Paradoxically, adiponectin induces TIMP-1 a pro- fibrogenic mediator. We are currently investigating the functional signifi- cance of adiponectin mediated TIMP-1 upregulation on HSC behaviour.

Item ID:	86239
Item Type:	Article (Abstract)
ISSN:	1440-1746
Related URLs:	https://doi.org/10.1111/j.1440-1746.2009...
Copyright Information:	© 2009 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Date Deposited:	21 Jul 2025 23:03
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320209 Gastroenterology and hepatology @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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