The anti-fibrotic effects of microRNA-153 by targeting TGFBR-2 in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic lung disease with an undefined etiology and no effective treatments. By binding to cell surface receptors, transforming growth factor-beta (TGF-beta) plays a pivotal role in lung fibrosis. Therefore, the screening of microRNAs (miRNAs), especially those interrupting the effects of TGF-beta, may provide information not only on the pathomechanism, but also on the treatment of this disease. In the present study, we found that miR-153 expression was dysregulated in the lungs of mice with experimental pulmonary fibrosis and TGF-beta 1 decreased miR-153 expression in pulmonary fibroblasts. Moreover, increased miR-153 levels attenuated, whereas the knock down of miR-153 promoted the pro-fibrogenic activity of TGF-beta 1, and miR-153 reduced the contractile and migratory activities of fibroblasts. In addition, TGFBR2, a transmembrane serine/threonine kinase receptor for TGF-beta, was identified as a direct target of miR-153. Furthermore, by post-transcriptional regulation of the expression of TGEBR2, phosphorylation of SMAD2/3 was also influenced by miR-153. These data suggest that miR-153 disturbs TGF-beta 1 signal transduction and its effects on fibroblast activation, acting as an anti-fibrotic element in the development of pulmonary fibrosis. (C) 2015 Elsevier Inc. All rights reserved.