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HIF1α‐induced upregulation of KLF4 promotes migration of human vascular smooth muscle cells under hypoxia
Author(s) -
Shan Fabo,
Huang Zhizhong,
Xiong Renping,
Huang QingYuan,
Li Junxia
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28953
Subject(s) - klf4 , downregulation and upregulation , hypoxia (environmental) , vascular smooth muscle , microbiology and biotechnology , hypoxia inducible factors , small interfering rna , biology , cancer research , chemistry , transcription factor , endocrinology , rna , biochemistry , gene , smooth muscle , oxygen , sox2 , organic chemistry
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.