Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis.

摘要: Osteopontin (OPN) promotes hepatic fibrosis, and developing therapies targeting OPN expression in settings of injury holds promise. The polyphenol epigallocatechin-3-gallate (EGCG), found high concentrations green tea, downregulates through mRNA degradation, but the mechanism is unknown. Previous work has shown that microRNAs can decrease levels, other studies have EGCG modulates multiple microRNAs. In our study, we first demonstrated induces stellate cells to transform into an activated state. We then identified three which target mRNA: miR-181a, miR-10b, miR-221. vitro results show upregulates all microRNAs, are capable down regulating when administered alone. Interestingly, only miR-221 necessary for EGCG-mediated degradation inhibition reduces effects on cell function. vivo experiments thioacetamide (TAA)-induced cytotoxicity expression; treatment with blocks TAA. Furthermore, chronic equally, suggesting more involved modulating expression. conclude models TAA-induced inhibits OPN-dependent fibrosis. works primarily by upregulating accelerate degradation. may therefore utility as a protective agent liver injury.