سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Sun, Dong, Wang, Haichang, Su, Yanhui, Lin, Jie, Zhang, Mingming, Man, Wanrong, Song, Xinglong, Zhang, Liang, Guo, Baolin, Hao, Kaikai, Sun, Dongdong. (1399). Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway. , 24(2), 150-159. doi: 10.22038/ijbms.2020.50808.11564
Dong Sun; Haichang Wang; Yanhui Su; Jie Lin; Mingming Zhang; Wanrong Man; Xinglong Song; Liang Zhang; Baolin Guo; Kaikai Hao; Dongdong Sun. "Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway". , 24, 2, 1399, 150-159. doi: 10.22038/ijbms.2020.50808.11564
Sun, Dong, Wang, Haichang, Su, Yanhui, Lin, Jie, Zhang, Mingming, Man, Wanrong, Song, Xinglong, Zhang, Liang, Guo, Baolin, Hao, Kaikai, Sun, Dongdong. (1399). 'Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway', , 24(2), pp. 150-159. doi: 10.22038/ijbms.2020.50808.11564
Sun, Dong, Wang, Haichang, Su, Yanhui, Lin, Jie, Zhang, Mingming, Man, Wanrong, Song, Xinglong, Zhang, Liang, Guo, Baolin, Hao, Kaikai, Sun, Dongdong. Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway. , 1399; 24(2): 150-159. doi: 10.22038/ijbms.2020.50808.11564

Exercise alleviates cardiac remodelling in diabetic cardiomyopathy via the miR-486a-5p-Mst1 pathway

Iranian Journal of Basic Medical Sciences
مقاله 4، دوره 24، شماره 2، اردیبهشت 2021، صفحه 150-159    اصل مقاله (1.55 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2020.50808.11564
نویسندگان
Dong Sun1، 2؛ Haichang Wang1، 3؛ Yanhui Su4؛ Jie Lin2؛ Mingming Zhang1؛ Wanrong Man2؛ Xinglong Song2؛ Liang Zhang2؛ Baolin Guo2؛ Kaikai Hao2؛ Dongdong Sun* 2
1Department of Cardiology, Tangdu Hospital, Air Force Medical University of PLA, Xi’an 710038, P.R. China
2Department of Cardiology, Xijing Hospital, Air Force Medical University of PLA, Xi’an 710032, P.R. China
3Heart Hospital, Xi’an International Medical Center, Xi’an 710100, P.R. China
4Department of Comprehensive Surgery of The Second Medical Center, General Hospital of Chinese People’s Liberation Army, Beijing 100853, P.R. China
چکیده
Objective(s): Physical exercise has emerged as an effective therapy to mitigate cardiac remodelling in diabetic cardiomyopathy (DCM). The results of our previous studies revealed mammalian sterile 20-like kinase 1 (Mst1) is a key regulator of the progression of DCM. However, the precise molecular mechanism of physical exercise-induced cardiac protection and its association with Mst1 inhibition remain unclear.
Materials and Methods: Wildtype and Mst1 transgenic mice were challenged with streptozotocin (STZ) to induce experimental diabetes and were divided into sedentary and exercise groups. The DCM phenotype was evaluated by echocardiography, Masson’s trichrome staining, TUNEL and immunoblotting analyses. The exercise-regulated miRNAs targeting Mst1 were predicted by bioinformatic analysis and later confirmed by RT-qPCR, immunoblotting, and dual-luciferase reporter assays. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulate diabetes to elucidate the underlying mechanisms.
Results: Compared to the sedentary diabetic control, physical exercise inhibited Mst1 and alleviated cardiac remodelling in mice with DCM, as evidenced by decreases in the left ventricular end-systolic internal dimension (LVESD) and left ventricular end-diastolic internal dimension (LVEDD), increases in the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), attenuation of collagen deposition, and the suppression of apoptosis. Bioinformatic analysis and apoptosis assessments revealed exercise exerted protective effects against DCM through miR-486a-5p release. Moreover, luciferase reporter assays confirmed miR-486a-5p directly suppressed the expression of Mst1, thereby inhibiting the apoptosis of cardiomyocytes subjected to high glucose treatment.
Conclusion: Physical exercise inhibits cardiac remodelling in DCM, and the mechanism is associated with miR-486a-5p release-induced Mst1 inhibition.
کلیدواژه‌ها
Apoptosis Diabetic cardiomyopathy Exercise Mst1 (STK4) miR؛ 486a؛ 5p
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