Qiu Feng, Tong Huijuan, Wang Yawen, Tao Jun, Wang Hailin, Chen Lei
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.
Biosci Biotechnol Biochem. 2018 Aug;82(8):1366-1376. doi: 10.1080/09168451.2018.1459179. Epub 2018 Apr 15.
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.
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。