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miR-21 对冠心病血管平滑肌细胞增殖、凋亡及炎症损伤的调控作用。

Modulation of Vascular Smooth Muscle Cell Multiplication, Apoptosis, and Inflammatory Damage by miR-21 in Coronary Heart Disease.

机构信息

Health Care Clinic, Qingdao Municipal Hospital (Group), Qingdao, Shandong 266071, China.

出版信息

Comput Math Methods Med. 2021 Nov 27;2021:6942699. doi: 10.1155/2021/6942699. eCollection 2021.

Abstract

This study is aimed at exploring the role and potential molecular mechanism of microRNA-21 (miR-21) in coronary heart disease (CHD). RT-qPCR analysis was conducted to detect the expression of miR-21, Sprouty 1 (SPRY1), and connexin 43 (CX43). The protein expression of SPRY1 and CX43 was measured by western blot. ELISA was performed for measuring inflammatory factors, including intercellular adhesion molecule-1 (ICAM-1) and interleukin-1 beta (IL-1). The target relationship between miR-21 and SPRY1 was determined by dual-luciferase reporter assay. Cell multiplication and apoptosis were detected using CCK-8 assay and flow cytometry analysis, respectively. Our results indicated that miR-21, CX43, and the level of inflammatory cytokines including ICAM-1 and IL-1 were upregulated, while SPRY1 was downregulated in blood samples from CHD patients compared with the controls. Besides, miR-21 directly targeted SRPY-1. miR-21 could suppress SPRY1 expression and enhance CX43 expression in VSMCs. Moreover, miR-21 accelerated cell multiplication and attenuated cell apoptosis in VSMCs. Collectively, these findings suggested that miR-21 could effectively elevate VSMC multiplication and repress apoptosis by targeting SPRY1 in CHD, providing a potential target for therapeutic strategy of CHD.

摘要

本研究旨在探讨 microRNA-21(miR-21)在冠心病(CHD)中的作用和潜在分子机制。通过 RT-qPCR 分析检测 miR-21、Spouty 1(SPRY1)和连接蛋白 43(CX43)的表达。通过 Western blot 测定 SPRY1 和 CX43 的蛋白表达。通过 ELISA 测定炎症因子,包括细胞间黏附分子-1(ICAM-1)和白细胞介素-1β(IL-1)。通过双荧光素酶报告基因测定确定 miR-21 和 SPRY1 之间的靶向关系。通过 CCK-8 测定和流式细胞术分析分别检测细胞增殖和细胞凋亡。我们的结果表明,与对照组相比,冠心病患者的血液样本中 miR-21、CX43 和包括 ICAM-1 和 IL-1 在内的炎症因子水平上调,而 SPRY1 下调。此外,miR-21 可直接靶向 SRPY-1。miR-21 可抑制 VSMCs 中 SPRY1 的表达并增强 CX43 的表达。此外,miR-21 可加速 VSMCs 的增殖并抑制细胞凋亡。总之,这些发现表明,miR-21 可通过靶向 SPRY1 有效增加 CHD 中 VSMC 的增殖并抑制细胞凋亡,为 CHD 的治疗策略提供了一个潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9883/8643245/adddb6a8abda/CMMM2021-6942699.001.jpg

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