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- Title
Morphogens and hepatic stellate cell fate regulation in chronic liver disease.
- Authors
Tsukamoto, Hidekazu; Zhu, Nian-Ling; Wang, Jiaohong; Asahina, Kinji; Machida, Keigo
- Abstract
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.
- Subjects
LIVER cancer; LIVER regeneration; MORPHOGENESIS; WOUND care; CARRIER proteins
- Publication
Journal of Gastroenterology & Hepatology, 2012, Vol 27, p94
- ISSN
0815-9319
- Publication type
Article
- DOI
10.1111/j.1440-1746.2011.07022.x