Abstract
In response to vascular injury or alterations in the local environment, such as hypoxia and hypertension, contractile vascular smooth muscle cells (VSMCs) are able to switch to a synthetic phenotype characterized by increased extracellular matrix synthesis with decreased expression of contractile markers. miR-182-5p has recently been reported to play a regulatory role in VSMCs proliferation. However, little is known about its target genes and related pathways in VSMCs phenotypic switch. Here, we investigated the function of miR-182-5p in VSMCs phenotypic switch. The results showed that upregulation of miR-182-5p promoted the switching of VSMCs from a contractile to a synthetic phenotype under hypoxic conditions. Mechanistically, hypoxia elevated miR-182-5p, leading to a reduction in expression of contractile markers and weakened RhoA signaling. Using bioinformatics analysis, dual-luciferase reporter assays and rescue assays, we demonstrated that miR-182-5p suppressed RhoA signaling by targeting RGS5. Collectively, the results from the present study indicated that miR-182-5p/RGS5/RhoA axis regulated hypoxia-induced VSMCs phenotypic switch.