Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage

The present research was designed to examine the effects of disintegrin metalloproteinases 10 (ADAM10) on the doxorubicin (DOX)-induced dilated cardiomyopathy (DCM) and the mechanisms involved, with a focus on ADAM10-dependent cleavage of N-cadherin. The present study constructed recombinant lentivi...

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Autores principales:	Li Xiaoou, Pan Feng, He Bing, Fang Chengzhi
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	adam10 n-cadherin cell adhesion shedding dcm cardiac remodeling Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5744b737e63c4fcfb88d573a8ea310f3
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spelling	oai:doaj.org-article:5744b737e63c4fcfb88d573a8ea310f32021-12-05T14:10:41ZInhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage2391-541210.1515/biol-2021-0081https://doaj.org/article/5744b737e63c4fcfb88d573a8ea310f32021-08-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0081https://doaj.org/toc/2391-5412The present research was designed to examine the effects of disintegrin metalloproteinases 10 (ADAM10) on the doxorubicin (DOX)-induced dilated cardiomyopathy (DCM) and the mechanisms involved, with a focus on ADAM10-dependent cleavage of N-cadherin. The present study constructed recombinant lentiviral vectors expressing short hairpin RNA (shRNA) targeting the ADAM10 gene. H9C2 cells were treated with the recombinant lentivirus or GI254023 (an ADAM10 inhibitor). The expression level of N-cadherin and its C-terminal fragment1 (CTF1) was tested by western blotting and flow cytometry. The adhesion ability was analyzed using a plate adhesion model. Cardiac function and morphology were assessed in control and lentivirus-transfected rats with or without DOX treatment. The inhibition of ADAM10 activity significantly increased the expression of full-length N-cadherin on the cellular surface and reduced CTF1 generation in vivo and in vitro. The adhesion ability was also increased in ADAM10-knockdown H9C2 cells. Furthermore, DOX-induced myocardial dysfunction was ameliorated in rats transfected with ADAM10-shRNA lentivirus. These findings demonstrated that ADAM10 specifically cleaves N-cadherin in cardiomyocytes. ADAM10-induced N-cadherin cleavage results in changes in the adhesive behavior of cells. Therefore, ADAM10 may serve as a therapeutic target to reverse cardiac remodeling in DCM.Li XiaoouPan FengHe BingFang ChengzhiDe Gruyterarticleadam10n-cadherincell adhesionsheddingdcmcardiac remodelingBiology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 856-866 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adam10 n-cadherin cell adhesion shedding dcm cardiac remodeling Biology (General) QH301-705.5
spellingShingle	adam10 n-cadherin cell adhesion shedding dcm cardiac remodeling Biology (General) QH301-705.5 Li Xiaoou Pan Feng He Bing Fang Chengzhi Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
description	The present research was designed to examine the effects of disintegrin metalloproteinases 10 (ADAM10) on the doxorubicin (DOX)-induced dilated cardiomyopathy (DCM) and the mechanisms involved, with a focus on ADAM10-dependent cleavage of N-cadherin. The present study constructed recombinant lentiviral vectors expressing short hairpin RNA (shRNA) targeting the ADAM10 gene. H9C2 cells were treated with the recombinant lentivirus or GI254023 (an ADAM10 inhibitor). The expression level of N-cadherin and its C-terminal fragment1 (CTF1) was tested by western blotting and flow cytometry. The adhesion ability was analyzed using a plate adhesion model. Cardiac function and morphology were assessed in control and lentivirus-transfected rats with or without DOX treatment. The inhibition of ADAM10 activity significantly increased the expression of full-length N-cadherin on the cellular surface and reduced CTF1 generation in vivo and in vitro. The adhesion ability was also increased in ADAM10-knockdown H9C2 cells. Furthermore, DOX-induced myocardial dysfunction was ameliorated in rats transfected with ADAM10-shRNA lentivirus. These findings demonstrated that ADAM10 specifically cleaves N-cadherin in cardiomyocytes. ADAM10-induced N-cadherin cleavage results in changes in the adhesive behavior of cells. Therefore, ADAM10 may serve as a therapeutic target to reverse cardiac remodeling in DCM.
format	article
author	Li Xiaoou Pan Feng He Bing Fang Chengzhi
author_facet	Li Xiaoou Pan Feng He Bing Fang Chengzhi
author_sort	Li Xiaoou
title	Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
title_short	Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
title_full	Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
title_fullStr	Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
title_full_unstemmed	Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
title_sort	inhibition of adam10 ameliorates doxorubicin-induced cardiac remodeling by suppressing n-cadherin cleavage
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/5744b737e63c4fcfb88d573a8ea310f3
work_keys_str_mv	AT lixiaoou inhibitionofadam10amelioratesdoxorubicininducedcardiacremodelingbysuppressingncadherincleavage AT panfeng inhibitionofadam10amelioratesdoxorubicininducedcardiacremodelingbysuppressingncadherincleavage AT hebing inhibitionofadam10amelioratesdoxorubicininducedcardiacremodelingbysuppressingncadherincleavage AT fangchengzhi inhibitionofadam10amelioratesdoxorubicininducedcardiacremodelingbysuppressingncadherincleavage
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Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage

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