Nkx2-3 induces autophagy inhibiting proliferation and migration of vascular smooth muscle cells via AMPK/mTOR signaling pathway

被引：18

作者：

Zheng, Huajun ^{[1
,2
,3
]}

Zhai, Weicheng ^{[1
,2
,3
]}

Zhong, Chongbin ^{[1
,2
,3
]}

Hong, Qingqing ^{[1
,2
,3
]}

Li, Hekai ^{[1
,2
,3
]}

Rui, Bowen ^{[1
,2
,3
]}

Zhu, Xingxing ^{[1
,2
,3
]}

Que, Dongdong ^{[1
,2
,3
]}

Feng, Liyun ^{[1
,2
,3
]}

Yu, Bin ^{[1
,2
,3
]}

Huang, Guanlin ^{[1
,2
,3
]}

Yin, Jianlong ^{[1
,2
,3
]}

Li, Jiacheng ^{[1
,2
,3
]}

Yan, Jing ^{[1
,2
,3
]}

Yang, Pingzhen ^{[1
,2
,3
]}

机构：

[1] Southern Med Univ, Zhujiang Hosp, Dept Cardiol, Lab Heart Ctr, Guangzhou 510280, Guangdong, Peoples R China

[2] Zhujiang Hosp, Guangdong Prov Biomed Engn Technol Res Ctr Cardio, Heart Ctr, Guangzhou, Guangdong, Peoples R China

[3] Zhujiang Hosp, Sino Japanese Cooperat Platform Translat Res Hear, Heart Ctr, Guangzhou, Guangdong, Peoples R China

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2021年 / 236卷 / 11期

基金：

中国国家自然科学基金;

关键词：

AMPK; mTOR signaling pathway; autophagy; Nkx2‐ 3; proliferation and migration; vascular smooth muscle cell; MICE; ACTIVATION; GENE;

D O I：

10.1002/jcp.30400

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Vascular remodeling and restenosis are common complications after percutaneous coronary intervention. Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in intimal hyperplasia-induced vascular restenosis. NK2 Homeobox 3 (Nkx2-3), a critical member of Nkx family, is involved in tissue differentiation and organ development. However, the role of Nkx2-3 in VSMCs proliferation and migration remains unknown. In this study, we used carotid balloon injury model and platelet-derived growth factor-BB (PDGF)-treated VSMCs as in vivo and in vitro experimental models. EdU assay and CCK-8 assay were used to detect cell proliferation. Migration was measured by scratch test. Hematoxylin and eosin staining and immunohistochemistry staining were used to evaluate the intimal hyperplasia. The autophagy level was detected by fluorescent mRFP-GFP-LC3 in vitro and by transmission electron microscopy in vivo. It was shown that Nkx2-3 was upregulated both in balloon injured carotid arteries and PDGF-stimulated VSMCs. Adenovirus-mediated Nkx2-3 overexpression inhibited intimal hyperplasia after balloon injury, and suppressed VSMCs proliferation and migration induced by PDGF. Conversely, silencing of Nkx2-3 by small interfering RNA exaggerated proliferation and migration of VSMCs. Furthermore, we found that Nkx2-3 enhanced autophagy level, while the autophagy inhibitor 3-MA eliminated the inhibitory effect of Nkx2-3 on VSMCs proliferation and migration both in vivo and in vitro. Moreover, Nkx2-3 promoted autophagy in VSMCs by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. These results demonstrated for the first time that Nkx2-3 inhibited VSMCs proliferation and migration through AMPK/mTOR-mediated autophagy.

引用

页码：7342 / 7355

页数：14

共 42 条

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