MiR-29Mediates TGFβ1-induced Extracellular Matrix Synthesis Through Activation Of Wnt/β-catenin Pathway In Human Pulmonary Fibroblasts

PURPOSE:Transforming growth factor β1(TGFβ1) is very important in the synthesis and degradation of extra cellular matrix (ECM), and also in the mediation of human Pulmonary fibroblasts proliferation, and miR-29plays an important role in this process. In the present study, the effects of TGFβ1on the expression of miR-29and whether miR-29is involved in pro-survival signaling pathways mediated by TGFβ1were examined in human Pulmonary fibroblasts.METHODS AND RESULTS:Treatment of the human IMR-90with TGFβ1caused a decrease in the expression of miR-29a/b/c by real-time PCR analysis. TGFβ1stimulation increased cell proliferation, colony formation and upregulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFβ1-induced phenotype changes in IMR-90. Western blot analyses showed that TGFβ1treatment unchanged total protein expression levels of β-catenin, but phosphorylation of β-catenin and the expression levels of wnt3a and COL1A1were increased; and miR-29a/b/c mimics interfering blocked DKK1, wnt3a, and phosphorylation of β-catenin and decreased expression of COL1A1 after TGFβ1treatment.CONCLUSIONS:TGFβ1activated the wnt/β1-catenin pathway, and this activation was essential for the expression of miR-29in IMR-90. The results indicate a novel biological function of the wnt/β-catenin pathway in IMR-90. Elevated expression of miR-29may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human IMR-90.