Open Access

Role of blocking Adam10 hydrolysis site on n‑cadherin by single‑chain antibody in ventricular remodeling

  • Authors:
    • Xiaoou Li
    • Wei Huang
    • Bing He
    • Lirong Zhou
    • Xiaogang Huang
    • Baozhen Yao
  • View Affiliations

  • Published online on: August 28, 2017     https://doi.org/10.3892/etm.2017.5057
  • Pages: 4215-4223
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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November-2017
Volume 14 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Li X, Huang W, He B, Zhou L, Huang X and Yao B: Role of blocking Adam10 hydrolysis site on n‑cadherin by single‑chain antibody in ventricular remodeling. Exp Ther Med 14: 4215-4223, 2017
APA
Li, X., Huang, W., He, B., Zhou, L., Huang, X., & Yao, B. (2017). Role of blocking Adam10 hydrolysis site on n‑cadherin by single‑chain antibody in ventricular remodeling. Experimental and Therapeutic Medicine, 14, 4215-4223. https://doi.org/10.3892/etm.2017.5057
MLA
Li, X., Huang, W., He, B., Zhou, L., Huang, X., Yao, B."Role of blocking Adam10 hydrolysis site on n‑cadherin by single‑chain antibody in ventricular remodeling". Experimental and Therapeutic Medicine 14.5 (2017): 4215-4223.
Chicago
Li, X., Huang, W., He, B., Zhou, L., Huang, X., Yao, B."Role of blocking Adam10 hydrolysis site on n‑cadherin by single‑chain antibody in ventricular remodeling". Experimental and Therapeutic Medicine 14, no. 5 (2017): 4215-4223. https://doi.org/10.3892/etm.2017.5057