ExosomalLINC01005derived from oxidized low-density lipoprotein-treated endothelial cells regulates vascular smooth muscle cell phenotypic switch

被引：38

作者：

Zhang, Zhiliang ^{[1
]}

Yi, Dasong ^{[1
]}

Zhou, Jiamin ^{[1
]}

Zheng, Yaofu ^{[1
]}

Gao, Zhiming ^{[1
]}

Hu, Xiaoliang ^{[1
]}

Ying, Guoqiu ^{[1
]}

Peng, Xiaoping ^{[1
]}

Wen, Tong ^{[1
]}

机构：

[1] Nanchang Univ, Hypertens Res Inst Jiangxi Prov, Affiliated Hosp 1, Dept Cardiol, 17 Yongwaizheng St, Nanchang 330006, Jiangxi, Peoples R China

来源：

BIOFACTORS | 2020年 / 46卷 / 05期

基金：

中国国家自然科学基金;

关键词：

atherosclerosis; Kruppel-like factor 4; LINC01005; miR-128-3p; phenotype switch; vascular smooth muscle cells; DIFFERENTIATION; PROLIFERATION; DYSFUNCTION; EXPRESSION; LNCRNAS;

D O I：

10.1002/biof.1665

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phenotype switch of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis (AS). Endothelial cells can regulate VSMC phenotypic switch by secreting exosomes, crucial mediators of intracellular communication. This study aimed to determine whether exosomal LINC01005 from oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) plays a role in regulating VSMC phenotypic switch and to validate the underlying molecular mechanism. Exosomes were extracted from ox-LDL-treated HUVECs (ox-LDL-Exo) and then administered into VSMCs. VSMC phenotypic switch was assessed by determining VSMC phenotypic markers using western blot. VSMC cell proliferation and migration were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and wound healing assay, respectively. The interaction between miR-128-3p and LINC01005 or Kruppel-like factor 4 (KLF4) was analyzed by luciferase reporter assay. ox-LDL-Exo contained high expression of LINC01005. Inhibition of LINC01005 expression in ox-LDL-Exo abrogated the ox-LDL-Exo-induced VSMC phenotypic switch, proliferation, and migration. Furthermore, LINC01005 acted as a sponge of miR-128-3p to upregulate KLF4 expression. Moreover, miR-128-3p overexpression and KLF4 silencing in VSMCs attenuated the ox-LDL-Exo-induced VSMC phenotypic switch, proliferation, and migration. Collectively, exosomal LINC01005 from ox-LDL-treated HUVECs promotes VSMC phenotype switch, proliferation, and migration by regulating the miR-128-3p/KLF4 axis.

引用

页码：743 / 753

页数：11

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