Open AccessmiRNA-145 inhibits VSMC proliferation by targeting CD40
Author(s) -
Xin Guo,
Dai Li,
Min Chen,
Lei Chen,
Bikui Zhang,
Tian Wu,
Ren Guo
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep35302
Subject(s) - vascular smooth muscle , gene knockdown , microrna , cd40 , phenotype , cell growth , downregulation and upregulation , homocysteine , medicine , endocrinology , cancer research , chemistry , microbiology and biotechnology , biology , apoptosis , in vitro , smooth muscle , gene , biochemistry , cytotoxic t cell
Recent studies have demonstrated functions of miR-145 in vascular smooth muscle cells (VSMCs) phenotypes and vascular diseases. In this study, we aim to determine whether CD40 is involved in miR-145 mediated switch of VSMC phenotypes. In cultured VSMCs, the effects of miR-145 and CD40 on TNF-α, TGF-β, and Homocysteine (Hcy) induced cell proliferation were evaluated by over-expression of miR-145 or by siRNA-mediated knockdown of CD40. We also used ultrasound imaging to explore the effect of miR-145 on carotid artery intima-media thickness (CIMT) in atherosclerotic cerebral infarction (ACI) patients. The results showed 50 ng/mL TNF-α, 5 ng/mL TGF-β, and 500 μmol/L Hcy significantly increased the expression of CD40, both at mRNA and protein levels, and also induced the proliferation of VSMCs. We found that over-expression of miR-145 significantly inhibited the expression of CD40 and the differentiation of VSMCs, and over-expression of miR-145 decreased IL-6 levels in VSMC supernatants. In ACI patients, the lower expression of miR-145 was associated with thicker CIMT and higher levels of plasma IL-6. Our results suggest that the miR-145/CD40 pathway is involved in regulating VSMC phenotypes in TNF-α, TGF-β, and Hcy induced VSMCs proliferation model. Targeting miR-145/CD40 might be a useful strategy for treating atherosclerosis.