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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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.
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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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