title: Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways.
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.
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Ying-Zhe
authors.initials: YZ
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Xue-Xin
authors.initials: XX
authors.lastname: Jin
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Gen-Long
authors.initials: GL
authors.lastname: Xue
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Li
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Sun
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Qi-He
authors.initials: QH
authors.lastname: Huang
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Song
authors.affiliation: Department of Cardiology, The 3rd affiliated hospital of Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150081, P. R China.
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.|Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne.
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
authors.affiliation: Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Du
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Medicine Research, Ministry of Education; State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Pan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D058065:Diabetic Cardiomyopathies / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000235:genetics*; D004452:Echocardiography; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D013311:Streptozocin; D005947:Glucose