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miR- 210 Protects Renal Cell Against Hypoxia-induced Apoptosis by Targeting HIF-1 Alpha

Authors
Li-Li Liu, Dahu Li, Yun-Ling He, Yan-Zhao Zhou, Sheng-Hui Gong, Li-Ying Wu, Yong-Qi Zhao, Xin Huang, Tong Zhao, Lun Xu, Kui-Wu Wu, Ming-Gao Li, Ling-Ling Zhu, and Ming Fan
Abstract
The kidney is vulnerable to hypoxia-induced injury. One of the mechanisms underlying this phenomenon is cell apoptosis triggered by hypoxia-inducible factor-1- α (HIF-1α) activation. MicroRNA-210 (miR-210) is known to be induced by HIF-1α and can regulate various pathological processes, but its role in hypoxic kidney injury remains unclear. Here, in both rat systemic hypoxia and local kidney hypoxia models, we found miR-210 levels were upregulated significantly in injured kidney, especially in renal tubular cells. A similar increase was observed in hypoxia-treated human renal tubular HK-2 cells. We also verified that miR-210 can directly suppress HIF-1α expression by targeting the 3′ untranslated region of HIF-1α mRNA in HK-2 cells in severe hypoxia. Accordingly, miR-210 overexpression caused significant inhibition of the HIF-1α pathway and attenuated apoptosis caused by hypoxia, while miR-210 knockdown exerted the opposite effect. Taken together, our findings verify that miR-210 is involved in the molecular response in hypoxic kidney lesions in vivo and attenuates hypoxia-induced renal tubular cell apoptosis by targeting HIF-1α directly and suppressing HIF-1α pathway activation in vitro.
Volume
2017
Page Range
258-271
DOI
10.2119/molmed.2017.00013
Date Published
October 16, 2017
Article PDF
17_013_Liu.pdf11284 KB
Supplemental Data
17_013_Liu_Suppl.pdf273 KB
Keywords
Liu, He, Zhou, Gong, Huang, Zhao, Xu, Wu, Li, Zhu, Fan, hypoxia-induced injury, cell apoptosis, miR- 210, renal disease, Hypoxia-inducible factors, HIFs, HIF-1α
Article Type
Research Article