Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1

被引：0
作者：
Shu, Jin [2 ]
Shi, Jue [2 ]
Gu, Yiwen [2 ]
Deng, Lei [2 ]
Zhao, Chen [2 ]
Wu, Chun [2 ]
Zhao, Jiachen [2 ]
Wang, Haiya [1 ]
Jin, Li [2 ]
机构：
[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Gerontol, Sch Med, Shanghai 200023, Peoples R China
[2] Shibei Hosp Jingan Dist, Dept Gerontol, Shanghai 200443, Peoples R China
来源：
OPEN LIFE SCIENCES | 2023年 / 18卷 / 01期
关键词：
tissue inhibitor of metalloproteinases-1; myocardial fibrosis; levocarnitine; angiotensin II; LIVER FIBROSIS; CELLULAR MECHANISMS; DYSFUNCTION; ACTIVATION; STAT4;
D O I：
10.1515/biol-2022-0554
中图分类号：
Q [生物科学];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
This study aimed to explore the effects of tissue inhibitor of metalloproteinases-1 (TIMP-1) on levocarnitine (LC)-mediated regulation of angiotensin II (AngII)-induced myocardial fibrosis (MF) and its underlying mechanisms. H9C2 cells were treated with AngII for 24 h to induce fibrosis. The cells were then treated with LC or transfected with TIMP-1-OE plasmid/si-TIMP-1. Cell apoptosis, viability, migration, and related gene expression were analyzed. AngII treatment significantly upregulated Axl, alpha-SMA, and MMP3 expression (P < 0.05) and downregulated STAT4 and TIMP1 expression (P < 0.05) relative to the control levels. After transfection, cells with TIMP-1 overexpression/knockdown were successfully established. Compared with that of the control, AngII significantly inhibited cell viability and cell migration while promoting cell apoptosis (P < 0.05). LC and TIMP-1-OE transfection further suppressed cell viability and migration induced by Ang II and upregulated apoptosis, whereas si-TIMP-1 had the opposite effect. Furthermore, LC and TIMP-1-OE transfection downregulated Axl, AT1R, alpha-SMA, collagen III, Bcl-2, and MMP3 expression caused by AngII and upregulated caspase 3, p53, and STAT4 expression, whereas si-TIMP-1 had the opposite effect. TIMP-1 is therefore a potential therapeutic target for delaying MF progression.
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页数：14
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