MiR-29 Mediates TGFβ1-induced Extracellular Matrix Synthesis through Activation of Wnt/β-catenin Pat

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TGFβ1 is very important in the synthesis and degradation of extracellular matrix (ECM), and also in the mediation of human pulmonary fibroblasts proliferation, and miR-29 plays an important role in this process.In the present study, the effects of TGFβ1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFβ1 were examined in human pulmonary fibroblasts.Treatment of the human IMR-90 cells with TGFβ1 caused a decrease in the expression of miR-29a/b/c as determined by real-time PCR analysis.TGFβ1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1;transfecting with miR-29a/b/c mimics reverse TGFβ1-induced phenotype changes in IMR-90.Western blot analyses showed that TGFβ1 treatment unchanged total protein expression levels of β-catenin, but phosphorylation of β-catenin and the expression levels of wnt3a and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked DKK1, wnt3a, and phosphorylation of β-catenin and decreased expression of COL1A1 after TGFβ1 treatment.Our results showed that TGF31 activated the wnt/β-catenin pathway, and this activation was essential for the expression of miR-29 in IMR-90.The results indicate a novel biological function of the wnt/β-catenin pathway in IMR-90.Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human IMR-90.
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