MiR-29 mediates TGFβ 1-induced extracellular matrix synthesis through activation of Wnt/β -catenin pathway in human pulmonary fibroblasts.

BACKGROUND: 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. OBJECTIVE: 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. METHODS AND RESULTS: 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 TGFβ1 activated the wnt/β-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/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.