Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai, China.
Key Laboratory for High Altitude Medicine, Ministry of Education, Xining, Qinghai, China.
Cell Biol Int. 2022 Nov;46(11):1864-1875. doi: 10.1002/cbin.11883. Epub 2022 Aug 10.
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.
针对血管损伤或局部环境的改变，如缺氧和高血压，收缩型血管平滑肌细胞（VSMCs）能够转变为合成表型，其特征是细胞外基质合成增加，收缩标志物表达减少。miR-182-5p 最近被报道在 VSMCs 的增殖中发挥调节作用。然而，miR-182-5p 在 VSMCs 表型转换中的靶基因和相关途径知之甚少。在这里，我们研究了 miR-182-5p 在 VSMCs 表型转换中的功能。结果表明，miR-182-5p 的上调促进了 VSMCs 在缺氧条件下从收缩型向合成型的转变。在机制上，缺氧上调了 miR-182-5p，导致收缩标志物的表达减少和 RhoA 信号减弱。通过生物信息学分析、双荧光素酶报告基因检测和挽救实验，我们证明 miR-182-5p 通过靶向 RGS5 抑制 RhoA 信号。总之，本研究结果表明，miR-182-5p/RGS5/RhoA 轴调节缺氧诱导的 VSMCs 表型转换。
