Resistin mediates the hepatic stellate cell phenotype.


AIM To describe the role of resistin in liver fibrosis. METHODS For the in vivo animal study, Sprague Dawley rats were subjected to bile duct ligation (BDL) for 4 wk. Rat liver, adipose tissue (epididymal fat) and serum were analyzed for resistin expression. For the in vitro experiment, rat primary hepatic stellate cells (HSCs) and Kupffer cells (KCs) were used. HSCs were exposed to recombinant resistin, and collagen  I, transforming growth factor β1, α smooth muscle actin, tissue inhibitor of metalloproteinase 1 and connective tissue growth factor expression were analyzed. Resistin gene and protein expression was quantified as was the expression of pro-inflammatory cytokines including tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8 and monocyte chemotactic protein-1 (MCP-1). The effects of resistin on HSC proliferation, migration and apoptosis were determined. The effects of resistin on KCs were also investigated. RESULTS Following BDL, rat epididymal fat and serum rather than liver showed higher resistin expression compared to control rats. In liver, resistin was expressed in quiescent HSCs and KCs. Resistin treatment resulted in enhancement of TNFα, IL-6, IL-8 and MCP-1 gene expression and increased IL-6 and MCP-1 protein in HSCs. Resistin activated HSC phospho-MAPK/p38, and p38 inhibition diminished IL-6 and MCP-1 expression. Furthermore, resistin facilitated HSC proliferation and migration, but decreased apoptosis which was via an IL-6 and MCP-1 mechanism. Finally, resistin-induced transforming growth factor β1 from KCs enhanced HSC collagen  I expression. CONCLUSION Resistin directly and indirectly modulates HSC behavior towards a more pro-fibrogenic phenotype.

DOI: 10.3748/wjg.v19.i28.4475
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@article{Dong2013ResistinMT, title={Resistin mediates the hepatic stellate cell phenotype.}, author={Zhi-Xia Dong and Lin Su and Joanne M Brymora and Claire Bird and Qing Xie and Jacob George and Jianhua Wang}, journal={World journal of gastroenterology}, year={2013}, volume={19 28}, pages={4475-85} }