BACKGROUND: TGFβ 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 TGFβ 1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFβ 1 were examined in human pulmonary fibroblasts.
METHODS AND RESULTS: Treatment of the human IMR-90 cells with TGFβ 1 caused a decrease in the expression of miR-29a/b/c as determined by real-time PCR analysis. TGFβ 1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFβ 1-induced phenotype changes in IMR-90. Western blot analyses showed that TGFβ 1 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 TGFβ 1 treatment. Our results showed that TGFβ 1 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.
