HIF1α-induced upregulation of KLF4 promotes migration of human vascular smooth muscle cells under hypoxia |
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| Authors: | Fabo Shan Zhizhong Huang Renping Xiong Qing-Yuan Huang Junxia Li |
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| Institution: | 1. Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, P.R. China;2. Department of Cold Environmental Medicine, College of High Altitude Military Medicine, Army Medical University, Chongqing, P.R. China;3. State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, P.R. China |
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| Abstract: | Hypoxia-induced vascular smooth muscle cells (VSMCs) migration plays an important role in vascular remodeling and is implicated in vascular diseases, such as atherosclerosis and pulmonary hypertension. We previously observed the increased expression of krüppel-like factor 4 (KLF4) in VSMCs under hypoxia. However, whether the upregulation of KLF4 participates in hypoxia-induced VSMCs migration is still unknown. In this study, we demonstrated that KLF4 was an important player in the process of VSMCs migration under hypoxia since interference of KLF4 by small interfering RNA mostly dampened hypoxia-induced migration of VSMCs. In addition, using luciferase reporter and ChIP assays, we confirmed two hypoxia-inducible factor 1α (HIF1α) binding elements (located at -150 to -163 and -3922 to -3932) in the upstream regulatory region of klf4 locus and identified KLF4 as a novel direct target gene of HIF1α. Our findings unveil a novel regulatory mechanism that involves HIF1α-induced upregulation of KLF4, which plays a vital role in VSMCs migration under hypoxia. |
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| Keywords: | HIF1α hypoxia KLF4 migration VSMCs |
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