MiR-29 mediates TGFβ1-induced extracellular matrix synthesis through activation of Wnt/β-catenin pathway in human pulmonary fibroblasts

BACKGROUND: TGF beta 1 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. OBJECTIVE: In the present study, the effects of TGF beta 1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGF beta 1 were examined in human pulmonary fibroblasts. METHODS AND RESULTS: Treatment of the human IMR-90 cells with TGF beta 1 caused a decrease in the expression of miR-29a/b/c as determined by real-time PCR analysis. TGF beta 1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGF beta 1-induced phenotype changes in IMR-90. Western blot analyses showed that TGF beta 1 treatment unchanged total protein expression levels of beta-catenin, but phosphorylation of beta-catenin and the expression levels of wnt3a and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked DKK1, wnt3a, and phosphorylation of beta-catenin and decreased expression of COL1A1 after TGF beta 1 treatment. Our results showed that TGF beta 1 activated the wnt/beta-catenin pathway, and this activation was essential for the expression of miR-29 in IMR-90. CONCLUSIONS: The results indicate a novel biological function of the wnt/beta-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.