Li Tianbo, Liu Chencheng, Liu Lingchao, Xia Han, Xiao Yingbin, Wang Xuefeng, Wang Yong
Department of Cardiovascular Surgery, the Second Affiliated Hospital (Xinqiao Hospital) of Chinese People's Liberation Army Medical University, Chongqing, China.
Yonsei Med J. 2019 Apr;60(4):352-359. doi: 10.3349/ymj.2019.60.4.352.
Previous studies have confirmed that microRNAs play important roles in the pathogenesis of acute aortic dissection (AAD). Here, we aimed to explore the role of miR-145 and its regulatory mechanism in the pathogenesis of AAD.
AAD tissue samples were harvested from patients with aortic dissection and normal donors. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with miR-145 mimic/inhibitor or negative control mimic/inhibitor. Gene and protein expression was measured in human aortic dissection tissue specimens and VSMCs by qRT-PCR and Western blot. Luciferase reporter assay was applied to verify whether connective tissue growth factor (CTGF) was a direct target of miR-145 in VSMCs. Methyl thiazolyl tetrazolium assay was used to detect VSMC viability.
miR-145 expression was downregulated in aortic dissection tissues and was associated with the survival of patients with AAD. Overexpression of miR-145 promoted VSMC proliferation and inhibited cell apoptosis. Moreover, CTGF, which was increased in aortic dissection tissues, was decreased by miR-145 mimic and increased by miR-145 inhibitor. Furthermore, CTGF was confirmed as a target of miR-145 and could reverse the promotion effect of miR-145 on the progression of AAD.
miR-145 suppressed the progression of AAD by targeting CTGF, suggesting that a miR-145/CTGF axis may provide a potential therapeutic target for AAD.
既往研究已证实微小RNA在急性主动脉夹层(AAD)的发病机制中起重要作用。在此,我们旨在探讨miR-145在AAD发病机制中的作用及其调控机制。
从主动脉夹层患者和正常供体中获取AAD组织样本。用miR-145模拟物/抑制剂或阴性对照模拟物/抑制剂转染大鼠主动脉血管平滑肌细胞(VSMC)。通过qRT-PCR和蛋白质免疫印迹法检测人主动脉夹层组织标本和VSMC中的基因和蛋白表达。应用荧光素酶报告基因检测法验证结缔组织生长因子(CTGF)是否为VSMC中miR-145的直接靶点。采用甲基噻唑基四氮唑法检测VSMC活力。
miR-145在主动脉夹层组织中的表达下调,且与AAD患者的生存相关。miR-145的过表达促进VSMC增殖并抑制细胞凋亡。此外,主动脉夹层组织中升高的CTGF,在转染miR-145模拟物后降低,而在转染miR-145抑制剂后升高。此外,CTGF被证实为miR-145的靶点,并且可以逆转miR-145对AAD进展的促进作用。
miR-145通过靶向CTGF抑制AAD的进展,提示miR-145/CTGF轴可能为AAD提供潜在的治疗靶点。