| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 100 === MiR-122a is a tumor suppressor microRNA. Mice lacking miR-122a (Mir122-/-) are viable but develop temporally controlled steatohepatitis, fibrosis and hepatocellular carcinoma (HCC). How miR-122a regulates liver fibrosis is unclear. Liver fibrosis is a disease stimulated by multiple inflammatory mediators, such as Tgf-β1 and Il-6, which led to hepatic stellate cell (HSC) activation, collagen accumulation and up-regulation of matrix metalloproteinase (MMP) as well as tissue inhibitor of metalloproteinase (TIMP). Recently, we identified Klf6, a fibrogenic transcription factor as a novel miR-122a target gene. Krüppel-like factor 6 (Klf6) is reported to be associated with HSC activation and elevated level of Klf6 was detected in the fibrosis livers of both human and rodents. To characterize the roles of Klf6 in liver fibrosis of Mir122-/- mice, we investigated (i) the expression of Klf6 target genes and fibrosis associated genes in liver fibrosis under mir-122 deficiency. (ii) the molecular mechanism of Klf6-regulated liver fibrosis.
In Mir122a-/- livers, the expression levels of Klf6, Klf6 target genes and fibrosis associated genes as well as serum level of Tgf-β1 are much higher than that of the wild-type mice. In vivo silencing of Klf6 by the hydrodynamic injection effectively reduced the severity of liver fibrosis, the elevated serum levels of Tgf-β1 and the hallmarks of HSC activation. I integrated the experimental data to infer a new molecular mechanism of Klf6-regulated liver fibrosis. These results also confirm that Klf6 plays a very important role in liver fibrosis.
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