Open AccessMiR‐339 inhibits proliferation of pulmonary artery smooth muscle cell by targeting FGF signaling
Author(s) -
Chen Jidong,
Cui Xiaolei,
Li Li,
Qu Junle,
Raj J. Usha,
Gou Deming
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13441
Subject(s) - platelet derived growth factor receptor , cell growth , fibroblast growth factor , signal transduction , pulmonary artery , cancer research , microrna , downregulation and upregulation , mapk/erk pathway , pathogenesis , medicine , gene knockdown , smooth muscle , microbiology and biotechnology , biology , growth factor , receptor , cell culture , gene , biochemistry , genetics
Pulmonary artery hypertension ( PAH ) is a fatal disorder. Recent studies suggest that micro RNA (mi RNA ) plays an important role in regulating proliferation of pulmonary artery smooth muscle cells ( PASMC ), which underlies the pathology of PAH . However, the exact mechanism of action of mi RNA s remains elusive. In this study, we found that miR‐339 was highly expressed in the cardiovascular system and was downregulated by a group of cytokines and growth factors, especially PDGF ‐ BB and FGF 2. Functional analyses revealed that miR‐339 can inhibit proliferation of PASMC . Also, miR‐339 inhibited FGF 2‐induced proliferation, but had no effect on proliferation induced by PDGF ‐ BB . The fibroblast growth factor receptor substrate 2 ( FRS 2) was identified as a potential direct target of miR‐339. Consistent with the actions of miR‐339, knockdown of FRS 2 only inhibited FGF 2‐ but not PDGF ‐ BB ‐induced proliferation of PASMC . In addition, our results showed that inhibition of ERK and PI 3K abrogated the downregulation of miR‐339 induced by PDGF ‐ BB . Finally, miR‐339 expression was found to be decreased in the pulmonary arteries of rats with MCT ‐induced PAH . Our study is the first report on the biological role of miR‐339 in regulating proliferation of PASMC by targeting FGF signaling, providing new mechanistic insights into PASMC proliferation and pathogenesis of PAH .