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J Mol Cell Cardiol. 2018 Feb;115:64-72. doi: 10.1016/j.yjmcc.2018.01.001. Epub 2018 Jan 3.

Ablation of interleukin-17 alleviated cardiac interstitial fibrosis and improved cardiac function via inhibiting long non-coding RNA-AK081284 in diabetic mice.

Author information

1
Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
2
Department of Cardiology, The 3rd affiliated hospital of Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150081, PR China.
3
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
4
Institute of Clinical Pharmacology, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road, Harbin, Heilongjiang, PR China.
5
Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. Electronic address: yjlu@hrbmu.edu.cn.
6
Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. Electronic address: panzw@ems.hrbmu.edu.cn.

Abstract

Interleukin 17 (IL-17) plays an important role in the pathogenesis of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-17 in the development of diabetic cardiomyopathy and the underlying mechanisms. The level of IL-17 increased in both the serum and cardiac tissue of diabetic mice. Knockout of IL-17 improved cardiac function of diabetic mice induced by streptozotocin (STZ), and significantly alleviated interstitial fibrosis as manifested by reduced collagen mRNA expression and collagen deposition evaluated by Masson's staining. High glucose treatment induced collagen production were abolished in cultured IL-17 knockout cardiac fibroblasts (CFs). The levels of long noncoding RNA-AK081284 were increased in the CFs treated with high glucose or IL-17. Knockout of IL-17 abrogated high glucose induced upregulation of AK081284. Overexpression of AK081284 in cultured CFs promoted the production of collagen and TGFβ1. Both high glucose and IL-17 induced collagen and TGFβ1 production were mitigated by the application of the siRNA for AK081284. In summary, deletion of IL-17 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The IL-17/AK081284/TGFβ1 signaling pathway mediates high glucose induced collagen production. This study indicates the therapeutic potential of IL-17 inhibition on diabetic cardiomyopathy disease associated with fibrosis.

KEYWORDS:

Diabetic cardiomyopathy; Interleukin-17; Interstitial fibrosis; Long noncoding RNA

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