Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans
Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans
复制标题
Mir-22-3p 通过靶向动脉硬化闭塞症中的 HMGB1 抑制动脉平滑肌细胞增殖和迁移以及新内膜增生
DOI：
10.1159/000480212
复制
发表时间：
2017-01-01
影响因子：
--
通讯作者：
Wang, Shen-ming
中科院分区：
文献类型：
--
作者：
Huang, Shui-chuan;Wang, Mian;Wang, Shen-ming
背景资料：异常的血管平滑肌细胞（VSMC）增殖和迁移有助于血管病理学的发展，例如动脉粥样硬化和血管成形术后再狭窄。本研究的目的是确定miR-22- 3 p是否在调节人动脉血管平滑肌细胞（HASMC）功能和新生内膜形成中发挥作用。方法：采用实时荧光定量PCR（qRT-PCR）和荧光原位杂交（FISH）技术检测人动脉组织中miR-22- 3 p的表达。进行细胞计数试剂盒-8（CCK-8）和EdU测定以评估细胞增殖，并进行transwell和伤口闭合测定以评估细胞迁移。此外，进行荧光素酶报告基因测定以鉴定miR-22- 3 p的靶基因。最后，使用大鼠颈动脉球囊损伤模型来确定miR-22- 3 p在新生内膜形成中的作用。结果如下：与正常动脉相比，动脉硬化闭塞症（阿索）动脉中miR-22- 3 p表达下调，与对照细胞相比，血小板源性生长因子-BB（PDGF-BB）刺激的HASMCs中miR-22- 3 p表达下调。miR-22- 3 p过表达具有抗增殖和抗迁移作用，双荧光素酶检测显示miR-22- 3 p直接作用于HASMCs中高迁移率族蛋白B1（HMGB 1）。此外，在阿索组织标本中，miR-22- 3 p表达与HMGB 1表达呈负相关。最后，LV-miR-22- 3 p介导的miR-22- 3 p上调通过减少体内HMGB 1表达显着抑制新生内膜增生。结论：miR-22- 3 p是一种S. Huang和M.王先生对这项工作作出了同样的贡献。通过靶向HMGB 1调节HASMC增殖和迁移关键分子以及miR-22- 3 p和HMGB 1可能是治疗人阿索的治疗靶点。(C)2017作者由S Karger AG，巴塞尔出版
Background: Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation. Methods:Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. Results: MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. Conclusions: Our results indicate that miR-22-3p is a S. Huang and M. Wang are contributted equally to this work. key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO. (C) 2017 The Author(s) Published by S Karger AG, Basel