LSD1 downregulates p21 expression in vascular smooth muscle cells and promotes neointima formation

被引：10

作者：

Yuan, Baohui ^{[1
,2
]}

Liu, He ^{[1
,2
]}

Pan, Xiaohua ^{[1
,2
]}

Dong, Xiaoliang ^{[1
,2
]}

Qu, Le-Feng ^{[3
]}

Sun, Jia ^{[1
,2
]}

Pan, Li-Long ^{[1
,2
]}

机构：

[1] Jiangnan Univ, Wuxi Sch Med, Wuxi, Jiangsu, Peoples R China

[2] Jiangnan Univ, Sch Food Sci & Technol, Wuxi, Jiangsu, Peoples R China

[3] Naval Med Univ, Changzheng Hosp, Dept Vasc & Endovasc Surg, Shanghai, Peoples R China

来源：

BIOCHEMICAL PHARMACOLOGY | 2022年 / 198卷

基金：

中国国家自然科学基金;

关键词：

Lysine-specific demethylase 1; Neointima formation; P21; Vascular smooth muscle cell; PROLIFERATION; CANCER;

D O I：

10.1016/j.bcp.2022.114947

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Neointima formation is characterized by the proliferation of vascular smooth muscle cells (VSMC). Although lysine-specific demethylase 1 (LSD1) has critical functions in several diseases, its role in neointima formation remains to be clarified. In this study, we aimed to explore the crucial role of LSD1 on neointima formation using a carotid artery injury model in mice. We observed that aberrant LSD1 expression was increased in human and mouse stenotic arteries and platelet-derived growth factor-BB (PDGF-BB)-treated VSMC. Furthermore, LSD1 knockdown significantly mitigated neointima formation in vivo and inhibited PDGF-BB-induced VSMC proliferation in vitro. We further uncovered that LSD1 overexpression exhibited opposite phenotypes in vivo and in vitro. Finally, LSD1 knockdown inhibited VSMC proliferation by increasing p21 expression, which is associated with LSD1 mediated di-methylated histone H3 on lysine 4 (H3K4me2) modification. Taken together, our data suggest that LSD1 may be a potential therapeutic target for the treatment of neointima formation.

引用

页数：11

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