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The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-βR1 signalling pathway.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-08-11 , DOI: 10.1002/jcp.29993
Xianglan Liu 1 , Shufeng Li 2, 3 , Yi Yang 2, 3 , Yong Sun 2, 3 , Qingyuan Yang 2, 3 , Nan Gu 2, 3 , Jing Li 2, 3 , Tuo Huang 2, 3 , Ying Liu 2, 3 , Hui Dong 2, 3 , Song Sun 4 , Guosheng Fu 1 , Jian Wu 2, 3 , Bo Yu 2, 3
Affiliation  

The long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) plays a critical role in the development of atherosclerosis. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated ANRIL expression in patients with coronary artery disease and elucidated the molecular mechanism underlying its effect. ANRIL expression was detected in the blood plasma of 111 patients. We analysed the correlation between ANRIL and endothelial dysfunction markers. We also examined the effect of ANRIL on the regulation of endothelial dysfunction. ANRIL levels were increased in patients with acute coronary syndrome. The expression of ANRIL is associated with the inflammatory cytokines monocyte chemoattractant protein‐1 and interleukin‐10, which are secreted in response to endothelial dysfunction. Knockdown of ANRIL significantly promoted cell proliferation and tubule formation and inhibited inflammatory activation and apoptosis of human umbilical vein endothelial cells (HUVEC). ANRIL‐mediated inhibition of let‐7b regulates HUVEC dysfunction by targeting the TGF‐βR1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.

中文翻译:

lncRNA ANRIL 通过靶向 let-7b/TGF-βR1 信号通路调节内皮功能障碍。

INK4 基因座 (ANRIL) 中的长链非编码 RNA 反义非编码 RNA 在动脉粥样硬化的发展中起关键作用。然而,ANRIL 对内皮功能障碍的确切影响仍不清楚。在这项研究中,我们调查了冠状动脉疾病患者中 ANRIL 的表达,并阐明了其影响的分子机制。在 111 名患者的血浆中检测到 ANRIL 表达。我们分析了 ANRIL 与内皮功能障碍标志物之间的相关性。我们还检查了 ANRIL 对内皮功能障碍调节的影响。急性冠脉综合征患者的 ANRIL 水平升高。ANRIL 的表达与炎症细胞因子单核细胞趋化蛋白 1 和白细胞介素 10 相关,它们是响应于内皮功能障碍而分泌的。敲除 ANRIL 可显着促进细胞增殖和小管形成,并抑制人脐静脉内皮细胞 (HUVEC) 的炎症激活和凋亡。ANRIL 介导的 let-7b 抑制通过靶向 TGF-βR1/Smad 信号通路调节 HUVEC 功能障碍。这项研究强调了一种预防与心血管疾病相关的内皮功能障碍的新治疗策略。
更新日期:2020-08-11
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