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EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation

Although EHMT2 (also known as G9a) plays a critical role in several kinds of cancers and cardiac remodeling, its function in vascular smooth muscle cells (VSMCs) remains unknown. In the present study, we revealed a novel function of EHMT2 in regulating autophagic cell death (ACD) of VSMC. Inhibition...

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Autores principales: Chen, Tai-Qiang, Hu, Nan, Huo, Bo, Masau, Jackson Ferdinand, Yi, Xin, Zhong, Xiao-Xuan, Chen, Yong-Jie, Guo, Xian, Zhu, Xue-Hai, Wei, Xiang, Jiang, Ding-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053323/
https://www.ncbi.nlm.nih.gov/pubmed/32174799
http://dx.doi.org/10.7150/ijbs.38835
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author Chen, Tai-Qiang
Hu, Nan
Huo, Bo
Masau, Jackson Ferdinand
Yi, Xin
Zhong, Xiao-Xuan
Chen, Yong-Jie
Guo, Xian
Zhu, Xue-Hai
Wei, Xiang
Jiang, Ding-Sheng
author_facet Chen, Tai-Qiang
Hu, Nan
Huo, Bo
Masau, Jackson Ferdinand
Yi, Xin
Zhong, Xiao-Xuan
Chen, Yong-Jie
Guo, Xian
Zhu, Xue-Hai
Wei, Xiang
Jiang, Ding-Sheng
author_sort Chen, Tai-Qiang
collection PubMed
description Although EHMT2 (also known as G9a) plays a critical role in several kinds of cancers and cardiac remodeling, its function in vascular smooth muscle cells (VSMCs) remains unknown. In the present study, we revealed a novel function of EHMT2 in regulating autophagic cell death (ACD) of VSMC. Inhibition of EHMT2 by BIX01294 or knockdown of EHMT2 resulted in reduced VSMC numbers which were independent of proliferation and apoptosis. Interestingly, EHMT2 protein levels were significantly decreased in VSMCs treated with autophagic inducers. Moreover, more autophagic vacuoles and accumulated LC3II were detected in VSMCs treated with BIX01294 or lenti-shEHMT2 than their counterparts. Furthermore, we found that EHMT2 inhibited the ACD of VSMCs by suppressing autophagosome formation. Mechanistically, the pro-autophagic effect elicited by EHMT2 inhibition was associated with SQSTM1 and BECN1 overexpression. Moreover, these detrimental effects were largely nullified by SQSTM1 or BECN1 knockdown. More importantly, similar results were observed in primary human aortic VSMCs. Overall, these findings suggest that EHMT2 functions as a crucial negative regulator of ACD via decreasing SQSTM1 or BECN1 expression and that EHMT2 could be a potent therapeutic target for cardiovascular diseases (e.g., aortic dissection).
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spelling pubmed-70533232020-03-13 EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation Chen, Tai-Qiang Hu, Nan Huo, Bo Masau, Jackson Ferdinand Yi, Xin Zhong, Xiao-Xuan Chen, Yong-Jie Guo, Xian Zhu, Xue-Hai Wei, Xiang Jiang, Ding-Sheng Int J Biol Sci Research Paper Although EHMT2 (also known as G9a) plays a critical role in several kinds of cancers and cardiac remodeling, its function in vascular smooth muscle cells (VSMCs) remains unknown. In the present study, we revealed a novel function of EHMT2 in regulating autophagic cell death (ACD) of VSMC. Inhibition of EHMT2 by BIX01294 or knockdown of EHMT2 resulted in reduced VSMC numbers which were independent of proliferation and apoptosis. Interestingly, EHMT2 protein levels were significantly decreased in VSMCs treated with autophagic inducers. Moreover, more autophagic vacuoles and accumulated LC3II were detected in VSMCs treated with BIX01294 or lenti-shEHMT2 than their counterparts. Furthermore, we found that EHMT2 inhibited the ACD of VSMCs by suppressing autophagosome formation. Mechanistically, the pro-autophagic effect elicited by EHMT2 inhibition was associated with SQSTM1 and BECN1 overexpression. Moreover, these detrimental effects were largely nullified by SQSTM1 or BECN1 knockdown. More importantly, similar results were observed in primary human aortic VSMCs. Overall, these findings suggest that EHMT2 functions as a crucial negative regulator of ACD via decreasing SQSTM1 or BECN1 expression and that EHMT2 could be a potent therapeutic target for cardiovascular diseases (e.g., aortic dissection). Ivyspring International Publisher 2020-02-10 /pmc/articles/PMC7053323/ /pubmed/32174799 http://dx.doi.org/10.7150/ijbs.38835 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Chen, Tai-Qiang
Hu, Nan
Huo, Bo
Masau, Jackson Ferdinand
Yi, Xin
Zhong, Xiao-Xuan
Chen, Yong-Jie
Guo, Xian
Zhu, Xue-Hai
Wei, Xiang
Jiang, Ding-Sheng
EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation
title EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation
title_full EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation
title_fullStr EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation
title_full_unstemmed EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation
title_short EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation
title_sort ehmt2/g9a inhibits aortic smooth muscle cell death by suppressing autophagy activation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053323/
https://www.ncbi.nlm.nih.gov/pubmed/32174799
http://dx.doi.org/10.7150/ijbs.38835
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