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Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy.
J Cell Mol Med. 2018 02; 22(2):808-822.JC

Abstract

Emerging evidence indicates that irisin provides beneficial effects in diabetes. However, whether irisin influences the development of diabetic cardiomyopathy (DCM) remains unclear. Therefore, we investigated the potential role and mechanism of action of irisin in diabetes-induced myocardial dysfunction in mice. Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic mice were administered recombinant r-irisin (low or high dose: 0.5 or 1.5 μg/g body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood glucose levels in the diabetic mice. However, the results of echocardiographical and histopathological assays indicated that low-dose irisin treatment alleviated cardiac fibrosis and left ventricular function in the diabetic mice, whereas high-dose irisin failed to mitigate the ventricular function impairment and increased collagen deposition. The potential mechanism underlying the effect of low-dose irisin involved irisin-mediated inhibition of high glucose-induced endothelial-to-mesenchymal transition (EndMT); conversely, high-dose irisin treatment enhanced high glucose-induced MMP expression by stimulating MAPK (p38 and ERK) signalling and cardiac fibroblast proliferation and migration. Low-dose irisin alleviated DCM development by inhibiting high glucose-induced EndMT. By contrast, high-dose irisin disrupted normal MMP expression and induced cardiac fibroblast proliferation and migration, which results in excess collagen deposition. Thus, irisin can inhibit high glucose-induced EndMT and exert a dose-dependent bidirectional effect on DCM.

Authors+Show Affiliations

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong, China.Department of Cardiology, Second Hospital of Shandong University, Jinan, Shandong, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.Department of Cardiology, Second Hospital of Shandong University, Jinan, Shandong, China.Department of Medicine-Solna, Clinical Pharma Pharmacology, Karolinska University Hospital-Solna, Stockholm, Sweden.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29063670

Citation

Liu, Xue, et al. "Irisin Inhibits High Glucose-induced Endothelial-to-mesenchymal Transition and Exerts a Dose-dependent Bidirectional Effect On Diabetic Cardiomyopathy." Journal of Cellular and Molecular Medicine, vol. 22, no. 2, 2018, pp. 808-822.
Liu X, Mujahid H, Rong B, et al. Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy. J Cell Mol Med. 2018;22(2):808-822.
Liu, X., Mujahid, H., Rong, B., Lu, Q. H., Zhang, W., Li, P., Li, N., Liang, E. S., Wang, Q., Tang, D. Q., Li, N. L., Ji, X. P., Chen, Y. G., Zhao, Y. X., & Zhang, M. X. (2018). Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy. Journal of Cellular and Molecular Medicine, 22(2), 808-822. https://doi.org/10.1111/jcmm.13360
Liu X, et al. Irisin Inhibits High Glucose-induced Endothelial-to-mesenchymal Transition and Exerts a Dose-dependent Bidirectional Effect On Diabetic Cardiomyopathy. J Cell Mol Med. 2018;22(2):808-822. PubMed PMID: 29063670.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy. AU - Liu,Xue, AU - Mujahid,Haroon, AU - Rong,Bing, AU - Lu,Qing-Hua, AU - Zhang,Wei, AU - Li,Peng, AU - Li,Na, AU - Liang,Er-Shun, AU - Wang,Qi, AU - Tang,Dong-Qi, AU - Li,Nai-Lin, AU - Ji,Xiao-Ping, AU - Chen,Yu-Guo, AU - Zhao,Yu-Xia, AU - Zhang,Ming-Xiang, Y1 - 2017/10/23/ PY - 2017/02/11/received PY - 2017/07/25/accepted PY - 2017/10/25/pubmed PY - 2019/4/23/medline PY - 2017/10/25/entrez KW - diabetic cardiomyopathy KW - irisin KW - myocardial dysfunction SP - 808 EP - 822 JF - Journal of cellular and molecular medicine JO - J Cell Mol Med VL - 22 IS - 2 N2 - Emerging evidence indicates that irisin provides beneficial effects in diabetes. However, whether irisin influences the development of diabetic cardiomyopathy (DCM) remains unclear. Therefore, we investigated the potential role and mechanism of action of irisin in diabetes-induced myocardial dysfunction in mice. Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic mice were administered recombinant r-irisin (low or high dose: 0.5 or 1.5 μg/g body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood glucose levels in the diabetic mice. However, the results of echocardiographical and histopathological assays indicated that low-dose irisin treatment alleviated cardiac fibrosis and left ventricular function in the diabetic mice, whereas high-dose irisin failed to mitigate the ventricular function impairment and increased collagen deposition. The potential mechanism underlying the effect of low-dose irisin involved irisin-mediated inhibition of high glucose-induced endothelial-to-mesenchymal transition (EndMT); conversely, high-dose irisin treatment enhanced high glucose-induced MMP expression by stimulating MAPK (p38 and ERK) signalling and cardiac fibroblast proliferation and migration. Low-dose irisin alleviated DCM development by inhibiting high glucose-induced EndMT. By contrast, high-dose irisin disrupted normal MMP expression and induced cardiac fibroblast proliferation and migration, which results in excess collagen deposition. Thus, irisin can inhibit high glucose-induced EndMT and exert a dose-dependent bidirectional effect on DCM. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/29063670/Irisin_inhibits_high_glucose_induced_endothelial_to_mesenchymal_transition_and_exerts_a_dose_dependent_bidirectional_effect_on_diabetic_cardiomyopathy_ L2 - https://doi.org/10.1111/jcmm.13360 DB - PRIME DP - Unbound Medicine ER -