Deletion of Interleukin-6 Alleviated Interstitial Fibrosis in Streptozotocin-induced Diabetic Cardiomyopathy of Mice Through Affecting TGFβ1 and MiR-29 Pathways

Overview

Journal Sci Rep

Specialty Science

Date 2016 Mar 15

PMID 26972749

Citations 62

Authors

Yang Zhang

Jing-Hao Wang

Yi-Yuan Zhang

Ying-Zhe Wang

Jin Wang

Yue Zhao

Xue-Xin Jin

Gen-Long Xue

Peng-Hui Li

Yi-Lin Sun

Qi-He Huang

Xiao-Tong Song

Zhi-Ren Zhang

Xu Gao

Bao-Feng Yang

Zhi-Min Du

Zhen-Wei Pan

Affiliations

Soon will be listed here.

Abstract

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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