MicroRNA-15b/16 Attenuates Vascular Neointima Formation by Promoting the Contractile Phenotype of Vascular Smooth Muscle Through Targeting YAP.
نویسندگان
چکیده
OBJECTIVE To investigate the functional role of the microRNA (miR)-15b/16 in vascular smooth muscle (SM) phenotypic modulation. APPROACH AND RESULTS We found that miR-15b/16 is one of the most abundant mRs expressed in contractile vascular smooth muscle cells (VSMCs). However, when contractile VSMCs get converted to a synthetic phenotype, miR-15b/16 expression is significantly reduced. Knocking down endogenous miR-15b/16 in VSMCs attenuates SM-specific gene expression but promotes VSMC proliferation and migration. Conversely, overexpression of miR-15b/16 promotes SM contractile gene expression while attenuating VSMC migration and proliferation. Consistent with this, overexpression of miR-15b/16 in a rat carotid balloon injury model markedly attenuates injury-induced SM dedifferentiation and neointima formation. Mechanistically, we identified the potent oncoprotein yes-associated protein (YAP) as a downstream target of miR-15b/16 in VSMCs. Reporter assays validated that miR-15b/16 targets YAP's 3' untranslated region. Moreover, overexpression of miR-15b/16 significantly represses YAP expression, whereas conversely, depletion of endogenous miR-15b/16 results in upregulation of YAP expression. CONCLUSIONS These results indicate that miR-15b/16 plays a critical role in SM phenotypic modulation at least partly through targeting YAP. Restoring expression of miR-15b/16 would be a potential therapeutic approach for treatment of proliferative vascular diseases.
منابع مشابه
The induction of yes-associated protein expression after arterial injury is crucial for smooth muscle phenotypic modulation and neointima formation.
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ورودعنوان ژورنال:
- Arteriosclerosis, thrombosis, and vascular biology
دوره 35 10 شماره
صفحات -
تاریخ انتشار 2015