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Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways
Interleukin 6 (IL-6) has been shown to be an important regulator of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-6 in the development of diabetic cardiomyopathy and the underlying mechanisms. Cardiac function of IL-6 knockout mice was significantly improved and i...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789642/ https://www.ncbi.nlm.nih.gov/pubmed/26972749 http://dx.doi.org/10.1038/srep23010 |
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author | Zhang, Yang Wang, Jing-Hao Zhang, Yi-Yuan Wang, Ying-Zhe Wang, Jin Zhao, Yue Jin, Xue-Xin Xue, Gen-Long Li, Peng-Hui Sun, Yi-Lin Huang, Qi-He Song, Xiao-Tong Zhang, Zhi-Ren Gao, Xu Yang, Bao-Feng Du, Zhi-Min Pan, Zhen-Wei |
author_facet | Zhang, Yang Wang, Jing-Hao Zhang, Yi-Yuan Wang, Ying-Zhe Wang, Jin Zhao, Yue Jin, Xue-Xin Xue, Gen-Long Li, Peng-Hui Sun, Yi-Lin Huang, Qi-He Song, Xiao-Tong Zhang, Zhi-Ren Gao, Xu Yang, Bao-Feng Du, Zhi-Min Pan, Zhen-Wei |
author_sort | Zhang, Yang |
collection | PubMed |
description | Interleukin 6 (IL-6) has been shown to be an important regulator of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-6 in the development of diabetic cardiomyopathy and the underlying mechanisms. Cardiac function of IL-6 knockout mice was significantly improved and interstitial fibrosis was apparently alleviated in comparison with wildtype (WT) diabetic mice induced by streptozotocin (STZ). Treatment with IL-6 significantly promoted the proliferation and collagen production of cultured cardiac fibroblasts (CFs). High glucose treatment increased collagen production, which were mitigated in CFs from IL-6 KO mice. Moreover, IL-6 knockout alleviated the up-regulation of TGFβ1 in diabetic hearts of mice and cultured CFs treated with high glucose or IL-6. Furthermore, the expression of miR-29 reduced upon IL-6 treatment, while increased in IL-6 KO hearts. Overexpression of miR-29 blocked the pro-fibrotic effects of IL-6 on cultured CFs. In summary, deletion of IL-6 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The mechanism involves the regulation of IL-6 on TGFβ1 and miR-29 pathway. This study indicates the therapeutic potential of IL-6 suppression on diabetic cardiomyopathy disease associated with fibrosis. |
format | Online Article Text |
id | pubmed-4789642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47896422016-03-16 Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways Zhang, Yang Wang, Jing-Hao Zhang, Yi-Yuan Wang, Ying-Zhe Wang, Jin Zhao, Yue Jin, Xue-Xin Xue, Gen-Long Li, Peng-Hui Sun, Yi-Lin Huang, Qi-He Song, Xiao-Tong Zhang, Zhi-Ren Gao, Xu Yang, Bao-Feng Du, Zhi-Min Pan, Zhen-Wei Sci Rep Article Interleukin 6 (IL-6) has been shown to be an important regulator of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-6 in the development of diabetic cardiomyopathy and the underlying mechanisms. Cardiac function of IL-6 knockout mice was significantly improved and interstitial fibrosis was apparently alleviated in comparison with wildtype (WT) diabetic mice induced by streptozotocin (STZ). Treatment with IL-6 significantly promoted the proliferation and collagen production of cultured cardiac fibroblasts (CFs). High glucose treatment increased collagen production, which were mitigated in CFs from IL-6 KO mice. Moreover, IL-6 knockout alleviated the up-regulation of TGFβ1 in diabetic hearts of mice and cultured CFs treated with high glucose or IL-6. Furthermore, the expression of miR-29 reduced upon IL-6 treatment, while increased in IL-6 KO hearts. Overexpression of miR-29 blocked the pro-fibrotic effects of IL-6 on cultured CFs. In summary, deletion of IL-6 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The mechanism involves the regulation of IL-6 on TGFβ1 and miR-29 pathway. This study indicates the therapeutic potential of IL-6 suppression on diabetic cardiomyopathy disease associated with fibrosis. Nature Publishing Group 2016-03-14 /pmc/articles/PMC4789642/ /pubmed/26972749 http://dx.doi.org/10.1038/srep23010 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhang, Yang Wang, Jing-Hao Zhang, Yi-Yuan Wang, Ying-Zhe Wang, Jin Zhao, Yue Jin, Xue-Xin Xue, Gen-Long Li, Peng-Hui Sun, Yi-Lin Huang, Qi-He Song, Xiao-Tong Zhang, Zhi-Ren Gao, Xu Yang, Bao-Feng Du, Zhi-Min Pan, Zhen-Wei Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways |
title | Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways |
title_full | Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways |
title_fullStr | Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways |
title_full_unstemmed | Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways |
title_short | Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways |
title_sort | deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting tgfβ1 and mir-29 pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789642/ https://www.ncbi.nlm.nih.gov/pubmed/26972749 http://dx.doi.org/10.1038/srep23010 |
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