MicroRNA‐92a promotes vascular smooth muscle cell proliferation and migration through the ROCK/MLCK signalling pathway
Open Access
- 25 March 2019
- journal article
- research article
- Published by Wiley in Journal of Cellular and Molecular Medicine
- Vol. 23 (5), 3696-3710
- https://doi.org/10.1111/jcmm.14274
Abstract
To identify the interaction between known regulators of atherosclerosis, microRNA‐92a (miR‐92a), Rho‐associated coiled‐coil‐forming kinase (ROCK) and myosin light chain kinase (MLCK), we examined their expressions during proliferation and migration of platelet‐derived growth factor‐BB (PDGF‐BB)‐regulated vascular smooth muscle cells (VSMCs), both in vivo and in vitro. During the formation of atherosclerosis plaque in mice, a parallel increase in expression levels of MLCK and miR‐92a was observed while miR‐92a expression was reduced in ML‐7 (an inhibitor of MLCK) treated mice and in MLCK‐deficient VSMCs. In vitro results indicated that both MLCK and miR‐92a shared the same signalling pathway. Transfection of miR‐92a mimic partially restored the effect of MLCK's deficiency and antagonized the effect of Y27632 (an inhibitor of ROCK) on the down‐regulation of VSMCs activities. ML‐7 increased the expression of Kruppel‐like factor 4 (KLF4, a target of miR‐92a), and siRNA‐KLF4 increased VSMCs' activity level. Consistently, inhibition of either MLCK or ROCK enhanced the KLF4 expression. Moreover, we observed that ROCK/MLCK up‐regulated miR‐92a expression in VSMCs through signal transducer and activator of transcription 3 (STAT3) activation. In conclusion, the activation of ROCK/STAT3 and/or MLCK/STAT3 may up‐regulate miR‐92a expression, which subsequently inhibits KLF4 expression and promotes PDGF‐BB‐mediated proliferation and migration of VSMCs. This new downstream node in the ROCK/MLCK signalling pathway may offer a potential intervention target for treatment of atherosclerosis.Funding Information
- National Natural Science Foundation of China (30470394, 31070719, 31370800, 81402916)
- Department of Education of Liaoning Province (20072166, 2009A195, 2013023015)
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