RGMa promotes dedifferentiation of vascular smooth muscle cells into a macrophage-like phenotype in vivo and in vitro

作者全名："Yuan, Xiaofan; Xiao, Hongmei; Hu, Qingzhe; Shen, Guanru; Qin, Xinyue"

作者地址："[Yuan, Xiaofan; Xiao, Hongmei; Hu, Qingzhe; Shen, Guanru; Qin, Xinyue] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Yuan, XF (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：JOURNAL OF LIPID RESEARCH

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000873963100004

JCR分区：Q1

影响因子：6.5

年份：2022

卷号：63

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：RGMa; Slug; atherosclerosis; carotid artery ligation; neointima; dedifferentiation; VSMCs; oxidized LDL

摘要："Repulsive guidance molecule a (RGMa) is a glycosylphosphatidylinositol-anchored glycoprotein that has been demonstrated to influence inflammatory-related diseases in addition to regulating neuronal differentiation and survival during brain development. However, any function or mechanism of RGMa in dedifferentiation of contractile vascular smooth muscle cells (VSMCs) during inflammatory-related atherosclerosis is poorly understood. In the current study, we found that RGMa is expressed in VSMCs-derived macrophage-like cells from the fibrous cap of type V atherosclerotic plaques and the neointima of ligated carotid artery in ApoE(-/-) mice. We determined levels of RGMa mRNA and protein increased in oxidized LDL (ox-LDL)-induced VSMCs. Knockdown of RGMa, both in vivo and in vitro, inhibited the dedifferentiation of ox-LDLinduced VSMCs and their ability to proliferate and migrate, reduced the thickness of the neointima after ligation of the left common carotid artery in ApoE(-/-) mice. Additionally, we show RGMa promoted the dedifferentiation of VSMCs via enhancement of the role of transcription factor Slug. Slug knockdown reversed the dedifferentiation of ox-LDL-induced VSMCs promoted by RGMa overexpression. Thus, inhibition of RGMa may constitute a therapeutic strategy for atherosclerotic plaques prone to rupture and restenosis following mechanical injury."

基金机构："National Science Foundation of China; National Natural Science Foundation of China, China [82071338]"

基金资助正文："The authors gratefully acknowledge the financial supports by the National Science Foundation of China. This study is supported by the National Natural Science Foundation of China, China (grant no.: 82071338)."