Identification of a novel TGF-β-miR-122-fibronectin 1/serum response factor signaling cascade and its implication in hepatic fibrogenesis.

ABSTRACT: Transforming growth factor-β (TGF-β) is a potent cytokine that promotes the development of fibrogenic cells, stimulates the expression of fibrosis-related genes, and consequently results in hepatic fibrogenesis. The involvement of miRNAs in this process remains largely unknown. We showed that miR-122 was substantially expressed in hepatic stellate cells (HSCs) and fibroblasts, the major sources of fibrogenic cells in liver tissues. Notably, exposure to TGF-β led to significant downregulation of miR-122. Furthermore, reintroduction of miR-122 suppressed TGF-β-induced expression of fibrosis-related genes, including alpha smooth muscle actin (α-SMA), fibronectin 1 (FN1) and α1 type I collagen (COL1A1), in HSCs and fibroblasts. Subsequent mechanism investigations revealed that miR-122 directly

SUBMITTER: Zeng C 

PROVIDER: S-EPMC4494934 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature