Southern California Research Center for ALPD and Cirrhosis, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
J Gastroenterol Hepatol. 2012 Mar;27 Suppl 2(Suppl 2):94-8. doi: 10.1111/j.1440-1746.2011.07022.x.
Hepatic stellate cells (HSC) are the liver mesenchymal cell type which responds to hepatocellular damage and participates in wound healing. Although HSC myofibroblastic trans-differentiation (activation) is implicated in excessive extracellular matrix deposition, molecular understanding of this phenotypic switch from the viewpoint of cell fate regulation is limited. Recent studies demonstrate the roles of anti-adipogenic morphogens (Wnt, Necdin, Shh) in epigenetic repression of the HSC differentiation gene Pparγ as a causal event in HSC activation. These morphogens have positive cross-interactions which converge to epigenetic repression of Pparγ involving the methyl-CpG binding protein MeCP2. However, these morphogens expressed by activated HSC may also participate in cross-talk between HSC and hepatoblasts/hepatocytes to support liver regeneration, and their aberrant regulation may contribute to liver tumorigenesis. Implications of HSC-derived morphogens in these possibilities are discussed.
肝星状细胞（HSC）是肝脏间充质细胞类型，对肝细胞损伤有反应，并参与伤口愈合。虽然 HSC 肌成纤维细胞转分化（激活）与细胞外基质的过度沉积有关，但从细胞命运调控的角度来看，对这种表型转换的分子理解是有限的。最近的研究表明，抗脂肪生成形态发生素（Wnt、Necdin、Shh）在 HSC 分化基因 Pparγ的表观遗传抑制中的作用，作为 HSC 激活的一个因果事件。这些形态发生素具有正的相互作用，它们汇聚到涉及甲基-CpG 结合蛋白 MeCP2 的 Pparγ的表观遗传抑制。然而，由激活的 HSC 表达的这些形态发生素也可能参与 HSC 和肝母细胞/肝细胞之间的对话，以支持肝再生，其异常调节可能导致肝癌发生。讨论了 HSC 衍生的形态发生素在这些可能性中的作用。
