Anti-adipogenic regulation underlies hepatic stellate cell transdifferentiation.

摘要: Cirrhosis is the most important consequence of alcoholic liver disease for which transplantation only treatment option available. Transdifferentiation hepatic stellate cells (HSC) to myofibroblastic (MF) a central event in fibrogenesis, and understanding molecular mechanisms that underlie this cellular provides pivotal insights into development new therapeutic modalities cirrhosis. To end, authors proposed several years ago transdifferentiation quiescent HSC MF may be causally associated with transcriptional regulation known adipocyte-preadipocytic fibroblast dedifferentiation. In support notion, showed adipogenic transcription factors their downstream adipocyte specific genes are expressed abundantly expression profile lost HM. Further, gain-of-function manipulations such as peroxisome proliferator-activated receptor-gamma (PPAR-gamma) sterol regulatory element binding protein-1c have been shown reverse culture-induced HSC. The also demonstrated tumor necrosis factor-alpha Wnt, mediators anti-adipogenesis, suppress activity PPAR-gamma contribute HSC-MF transdifferentiation. These results reinforce concept essential phenotype loss underlying HSC-HM They provide basis use agonists, has advocated fibrosis.