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抑制miR-21-5p通过maspin调控AKT和ERK信号通路,从而抑制高糖诱导的人视网膜微血管内皮细胞增殖和血管生成。

Inhibition of miR-21-5p suppresses high glucose-induced proliferation and angiogenesis of human retinal microvascular endothelial cells by the regulation of AKT and ERK pathways via maspin.

作者信息

Qiu Feng, Tong Huijuan, Wang Yawen, Tao Jun, Wang Hailin, Chen Lei

机构信息

a Department of Ophthalmology , The First Affiliated Hospital of China Medical University , Shenyang , People's Republic of China.

b Department of Ophthalmology , Shenyang Fourth People's Hospital , Shenyang , People's Republic of China.

出版信息

Biosci Biotechnol Biochem. 2018 Aug;82(8):1366-1376. doi: 10.1080/09168451.2018.1459179. Epub 2018 Apr 15.

Abstract

The aim of the present study is to investigate the role of miR-21-5p in angiogenesis of human retinal microvascular endothelial cells (HRMECs). HRMECs were incubated with 5 mM glucose, 30 mM glucose or 30 mM mannitol for 24 h, 48 h or 72 h. Then, HRMECs exposed to 30 mM glucose were transfected with miR-21-5p inhibitor. We found that high glucose increased the expression of miR-21-5p, VEGF, VEGFR2 and cell proliferation activity. Inhibition of miR-21-5p reduced high glucose-induced proliferation, migration, tube formation of HRMECs, and reversed the decreased expression of maspin as well as the abnormal activation of PI3K/AKT and ERK pathways. Down-regulation of maspin by siRNA significantly increased the activities of PI3K/AKT and ERK pathways. In conclusion, inhibition of miR-21-5p could suppress high glucose-induced proliferation and angiogenesis of HRMECs, and these effects may partly dependent on the regulation of PI3K/AKT and ERK pathways via its target protein maspin.

摘要

本研究的目的是探讨miR-21-5p在人视网膜微血管内皮细胞(HRMECs)血管生成中的作用。将HRMECs分别用5 mM葡萄糖、30 mM葡萄糖或30 mM甘露醇孵育24小时、48小时或72小时。然后,用miR-21-5p抑制剂转染暴露于30 mM葡萄糖的HRMECs。我们发现高糖增加了miR-21-5p、VEGF、VEGFR2的表达以及细胞增殖活性。抑制miR-21-5p可降低高糖诱导的HRMECs增殖、迁移、管腔形成,并逆转maspin表达的降低以及PI3K/AKT和ERK通路的异常激活。通过siRNA下调maspin可显著增加PI3K/AKT和ERK通路的活性。总之,抑制miR-21-5p可抑制高糖诱导的HRMECs增殖和血管生成,这些作用可能部分依赖于通过其靶蛋白maspin对PI3K/AKT和ERK通路的调节。

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