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CD38 promotes angiotensin II‐induced cardiac hypertrophy
Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H(2)O(2)‐induced injury and hypox...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542907/ https://www.ncbi.nlm.nih.gov/pubmed/28296029 http://dx.doi.org/10.1111/jcmm.13076 |
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author | Guan, Xiao‐Hui Hong, Xuan Zhao, Ning Liu, Xiao‐Hong Xiao, Yun‐Fei Chen, Ting‐Tao Deng, Li‐Bin Wang, Xiao‐Lei Wang, Jian‐Bin Ji, Guang‐Ju Fu, Mingui Deng, Ke‐Yu Xin, Hong‐Bo |
author_facet | Guan, Xiao‐Hui Hong, Xuan Zhao, Ning Liu, Xiao‐Hong Xiao, Yun‐Fei Chen, Ting‐Tao Deng, Li‐Bin Wang, Xiao‐Lei Wang, Jian‐Bin Ji, Guang‐Ju Fu, Mingui Deng, Ke‐Yu Xin, Hong‐Bo |
author_sort | Guan, Xiao‐Hui |
collection | PubMed |
description | Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H(2)O(2)‐induced injury and hypoxia/reoxygenation‐induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs‐mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored. Here, we investigated the roles and mechanisms of CD38 in angiotensin II (Ang‐II)‐induced cardiac hypertrophy. Following 14 days of Ang‐II infusion with osmotic mini‐pumps, a comparable hypertension was generated in both of CD38 knockout and wild‐type mice. However, the cardiac hypertrophy and fibrosis were much more severe in wild‐type mice compared with CD38 knockout mice. Consistently, RNAi‐induced knockdown of CD38 decreased the gene expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and reactive oxygen species generation in Ang‐II‐stimulated H9c2 cells. In addition, the expression of SIRT3 was elevated in CD38 knockdown H9c2 cells, in which SIRT3 may further activate the FOXO3 antioxidant pathway. The intracellular Ca(2+) release induced by Ang‐II markedly decreased in CD38 knockdown H9c2 cells, which might be associated with the decrease of nuclear translocation of NFATc4 and inhibition of ERK/AKT phosphorylation. We concluded that CD38 plays an essential role in cardiac hypertrophy probably via inhibition of SIRT3 expression and activation of Ca(2+)‐NFAT signalling pathway. Thus, CD38 may be a novel target for treating cardiac hypertrophy. |
format | Online Article Text |
id | pubmed-5542907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55429072017-08-09 CD38 promotes angiotensin II‐induced cardiac hypertrophy Guan, Xiao‐Hui Hong, Xuan Zhao, Ning Liu, Xiao‐Hong Xiao, Yun‐Fei Chen, Ting‐Tao Deng, Li‐Bin Wang, Xiao‐Lei Wang, Jian‐Bin Ji, Guang‐Ju Fu, Mingui Deng, Ke‐Yu Xin, Hong‐Bo J Cell Mol Med Original Articles Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H(2)O(2)‐induced injury and hypoxia/reoxygenation‐induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs‐mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored. Here, we investigated the roles and mechanisms of CD38 in angiotensin II (Ang‐II)‐induced cardiac hypertrophy. Following 14 days of Ang‐II infusion with osmotic mini‐pumps, a comparable hypertension was generated in both of CD38 knockout and wild‐type mice. However, the cardiac hypertrophy and fibrosis were much more severe in wild‐type mice compared with CD38 knockout mice. Consistently, RNAi‐induced knockdown of CD38 decreased the gene expressions of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and reactive oxygen species generation in Ang‐II‐stimulated H9c2 cells. In addition, the expression of SIRT3 was elevated in CD38 knockdown H9c2 cells, in which SIRT3 may further activate the FOXO3 antioxidant pathway. The intracellular Ca(2+) release induced by Ang‐II markedly decreased in CD38 knockdown H9c2 cells, which might be associated with the decrease of nuclear translocation of NFATc4 and inhibition of ERK/AKT phosphorylation. We concluded that CD38 plays an essential role in cardiac hypertrophy probably via inhibition of SIRT3 expression and activation of Ca(2+)‐NFAT signalling pathway. Thus, CD38 may be a novel target for treating cardiac hypertrophy. John Wiley and Sons Inc. 2017-03-12 2017-08 /pmc/articles/PMC5542907/ /pubmed/28296029 http://dx.doi.org/10.1111/jcmm.13076 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Guan, Xiao‐Hui Hong, Xuan Zhao, Ning Liu, Xiao‐Hong Xiao, Yun‐Fei Chen, Ting‐Tao Deng, Li‐Bin Wang, Xiao‐Lei Wang, Jian‐Bin Ji, Guang‐Ju Fu, Mingui Deng, Ke‐Yu Xin, Hong‐Bo CD38 promotes angiotensin II‐induced cardiac hypertrophy |
title | CD38 promotes angiotensin II‐induced cardiac hypertrophy |
title_full | CD38 promotes angiotensin II‐induced cardiac hypertrophy |
title_fullStr | CD38 promotes angiotensin II‐induced cardiac hypertrophy |
title_full_unstemmed | CD38 promotes angiotensin II‐induced cardiac hypertrophy |
title_short | CD38 promotes angiotensin II‐induced cardiac hypertrophy |
title_sort | cd38 promotes angiotensin ii‐induced cardiac hypertrophy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542907/ https://www.ncbi.nlm.nih.gov/pubmed/28296029 http://dx.doi.org/10.1111/jcmm.13076 |
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