Department of Life Sciences, Incheon National University, Incheon 22012, Korea.
Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea.
Int J Mol Sci. 2020 Jul 4;21(13):4764. doi: 10.3390/ijms21134764.
Proliferation and migration of vascular smooth muscle cells (VSMCs) are implicated in blood vessel development, maintenance of vascular homeostasis, and pathogenesis of vascular disorders. MicroRNAs (miRNAs) mediate the regulation of VSMC functions in response to microenvironmental signals. Because a previous study reported that miR-101, a tumor-suppressive miRNA, is a critical regulator of cell proliferation in vascular disease, we hypothesized that miR-101 controls important cellular processes in VSMCs. The present study aimed to elucidate the effects of miR-101 on VSMC function and its molecular mechanisms. We revealed that miR-101 regulates VSMC proliferation and migration. We showed that miR-101 expression is induced by bone morphogenetic protein (BMP) signaling, and we identified dedicator of cytokinesis 4 (DOCK4) as a novel target of miR-101. Our results suggest that the BMP-miR-101-DOCK4 axis mediates the regulation of VSMC function. Our findings help further the understanding of vascular physiology and pathology.
血管平滑肌细胞(VSMCs)的增殖和迁移与血管发育、血管稳态的维持以及血管疾病的发病机制有关。微小 RNA(miRNA)介导 VSMC 功能对微环境信号的调节。由于先前的研究报告称,肿瘤抑制 miRNA miR-101 是血管疾病中细胞增殖的关键调节因子,因此我们假设 miR-101 控制 VSMCs 中的重要细胞过程。本研究旨在阐明 miR-101 对 VSMC 功能的影响及其分子机制。我们揭示了 miR-101 调节 VSMC 的增殖和迁移。我们表明,miR-101 的表达受骨形态发生蛋白(BMP)信号的诱导,并且我们鉴定出胞质分裂蛋白 4(DOCK4)是 miR-101 的一个新靶标。我们的结果表明,BMP-miR-101-DOCK4 轴介导了 VSMC 功能的调节。我们的研究结果有助于进一步了解血管生理学和病理学。