Yang Xiaoyan, Dong Mei, Wen Hao, Liu Xiaoling, Zhang Meng, Ma Lianyue, Zhang Cheng, Luan Xiaorong, Lu Huixia, Zhang Yun
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Oncotarget. 2017 May 18;8(44):75844-75853. doi: 10.18632/oncotarget.17998. eCollection 2017 Sep 29.
The phenotypic switch of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, such as atherosclerosis and post-angioplasty restenosis. Small non-coding microRNAs (miRNAs) have emerged as critical modulators of VSMC function. In the present study, miR-26a was significantly increased in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB) and in arteries with neointimal lesion formation. Moreover, we demonstrated that miR-26a regulates the expression of VSMC differentiation marker genes such as α-smooth muscle actin (α-SMA), calponin and smooth muscle myosin heavy chain (SM-MHC) in PDGF-BB-treated VSMCs. We further confirmed that the regulatory effect of miR-26a during the phenotypic transition occurs through its target gene Smad1, which is a critical mediator of the pro-contractile signal transmitted by bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-β). This discovery proposed a new channel for communication between PDGF and the BMP/TGF-β family. We concluded that miR-26a is an important regulator in the PDGF-BB-mediated VSMC phenotypic transition by targeting Smad1. Interventions aimed at miR-26a may be promising in treating numerous proliferative vascular disorders.
血管平滑肌细胞（VSMC）的表型转换是各种血管疾病（如动脉粥样硬化和血管成形术后再狭窄）发病机制中的关键事件。小型非编码微小RNA（miRNA）已成为VSMC功能的关键调节因子。在本研究中，miR-26a在血小板衍生生长因子-BB（PDGF-BB）刺激的培养VSMC以及形成新生内膜病变的动脉中显著增加。此外，我们证明miR-26a在PDGF-BB处理的VSMC中调节VSMC分化标记基因的表达，如α-平滑肌肌动蛋白（α-SMA）、钙调蛋白和平滑肌肌球蛋白重链（SM-MHC）。我们进一步证实，miR-26a在表型转变过程中的调节作用是通过其靶基因Smad1实现的，Smad1是骨形态发生蛋白（BMP）和转化生长因子-β（TGF-β）传递的促收缩信号的关键介质。这一发现提出了PDGF与BMP/TGF-β家族之间新的沟通渠道。我们得出结论，miR-26a通过靶向Smad1是PDGF-BB介导的VSMC表型转变中的重要调节因子。针对miR-26a的干预措施在治疗多种增殖性血管疾病方面可能具有前景。
