title: MicroRNA-24 inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1.
abstract: Dysfunction of vascular smooth muscle cells (VSMCs) performs a key role in the pathogenesis of diabetic vascular disease. Recent studies have reported that microRNA-24 (miR-24) may be implicated in diabetes and atherosclerotic vascular diseases. This study was designed to explore the role of miR-24 on VSMC proliferation and migration under high glucose conditions mimicking diabetes, and reveal the underlying mechanism. VSMCs were isolated from rat thoracic aortas, treated with normal glucose (NG, 5.5mM) or high glucose (HG, 30mM) during an incubation period. Cell viability, proliferation and migration were detected by trypan blue staining, BrdU incorporation assay and transwell chamber assay. Gene and protein expression were analyzed by qRT-PCR and Western blot respectively. We also used electrophoretic mobility shift assay (EMSA) to detect nuclear factor kappaB (NF-κB) DNA binding. TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay. The results showed that adenovirus-mediated miR-24 overexpression significantly inhibited HG-stimulated VSMC proliferation and migration. Meanwhile, high mobility group box-1 (HMGB1) as a target of miR-24, was also markedly suppressed after miR-24 transfection. Additionally, NF-κB nuclear translocation and DNA binding, TNF-α and IL-6 production were all decreased associated with the down-regulation of HMGB1. The above data indicated that miR-24 is a crucial regulator of high glucose-induced proliferation and migration in VSMCs, and suggests that elevation of miR-24 in vascular system may be a novel therapeutic strategy to prevent the development of diabetic atherosclerosis.
authors.affiliation: Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Optometry and Ophthalmology, Yichang Central People's Hospital, Yichang 443000, Hubei Province, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Jiawang
authors.initials: J
authors.lastname: Ding
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Huibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China. Electronic address: yangjun@ctgu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D015850:Interleukin-6; C574736:MIRN24 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose
keywords: High mobility group box-1; Inflammation; MicroRNA-24; Migration; Proliferation; Vascular smooth muscle cell