Carnosol-mediated Sirtuin 1 activation inhibits Enhancer of Zeste Homolog 2 to attenuate liver fibrosis.

摘要: Quiescent hepatic stellate cell (HSC) activation and subsequent conversion into myofibroblasts is the central event in fibrosis pathogenesis. Epithelial-mesenchymal transition (EMT), another vital participant liver fibrosis, has potential to initiate HSC activation, which promotes abundant myofibroblast production. Previous studies suggest that Enhancer of Zeste Homolog 2 (EZH2) plays a significant role transdifferentiation; however, underlying mechanisms remain largely unaddressed. Carnosol (CS), compound extracted from rosemary, displays multiple pharmacological activities. This study aimed investigate signaling EZH2 inhibition anti-fibrotic effect CS fibrosis. We found significantly inhibited CCl4- TGFβ1-induced reduced both EMT. knockdown also prevented these processes induced by TGFβ1 HSCs AML-12 cells. Interestingly, protective was positively associated with Sirtuin 1 (SIRT1) accompanied inhibition. SIRT1 attenuated increased acetylation, enhanced its stability. Conversely, upon exposure, level acetylation; overexpression primed inhibition, indicating target SIRT1. Thus, SIRT1/EZH2 regulation could be used as new therapeutic strategy for fibrogenesis. Together, this provides evidence pathway inhibits generation, thus, may represent an attractive candidate clinical therapy.