Role of blocking ADAM10 hydrolysis site on N-cadherin by single-chain antibody in ventricular remodeling

被引:6
|
作者
Li, Xiaoou [1 ]
Huang, Wei [2 ]
He, Bing [1 ]
Zhou, Lirong [2 ]
Huang, Xiaogang [2 ]
Yao, Baozhen [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Pediat, 99 Zhang Zhi Dong St, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Inst Med Sci, Dept Preclin Med, 47 Li Huang Pi Rd, Wuhan 430014, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
N-cadherin; ADAM10 hydrolysis site; dilated cardiomyopathy; DILATED CARDIOMYOPATHY; CARDIOMYOCYTES; EXPRESSION; CONNEXIN-43; DYSFUNCTION; CLEAVAGE; ADHESION; CATENIN;
D O I
10.3892/etm.2017.5057
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The present study aimed to investigate the roles of the hydrolytic process of N-cadherin by A disintegrin and metalloproteases 10 (ADAM10) in sustaining myocardial structure and integrity, and discuss the mechanisms of ventricular remodeling in dilated cardiomyopathy (DCM). Single chain variable fragment antibody (ScFv) with the ability to specifically block the ADAM10 hydrolysis site of N-cadherin was designed and constructed. Western blot analysis and flow cytometry were used to detect the expression of N-cadherin and its C-terminal fragment 1 (CTF1) on cardiomyocytes, and cells were also subjected to a cell adhesion assay. Furthermore, in a rat model of dilated cardiomyopathy (DCM), the effects of intracardiac injection of the recombinant adenovirus on cardiac structure and contractile function were observed by hematoxylin and eosin staining and color Doppler echocardiography. The recombinant ScFv-expressing adenoviral plasmid with the ability to block the ADAM10 hydrolysis site on N-cadherin was successfully constructed and efficiently transfected into H9C2 cells. After transfection, N-cadherin protein expression was significantly increased, CTF1 protein was significantly decreased and the adhesion capability of myocardial cells was significantly improved. In the in vivo experiment, N-cadherin expression was significantly increased in the treatment group compared with that in the model group, and the structure and function of the heart were significantly improved. In conclusion, blocking of the ADAM10 hydrolysis site on N-cadherin by ScFv increased N-cadherin expression and improved ventricular remodeling. The present study provided experimental evidence for a novel approach for the treatment and prevention of DCM.
引用
收藏
页码:4215 / 4223
页数:9
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