Effects of microRNA-292-5p on myocardial ischemia–reperfusion injury through the peroxisome proliferator-activated receptor-α/-γ signaling pathway
Authors: Ji-Yun Ye
Zhong-Hua Xia
Xue-Mei Fu
Xuan Zhang
Zhen-Dong Zhu
Yu-Mei Ma
Hua Niu
Journal: Gene Therapy (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ischemia-reperfusion injury; microRNA-292-5p; myocardial IRI; peroxisome proliferator-activated receptor; PPAR-α
Affiliations: Department of Cardiovascular Diseases, The Third People's Hospital of Yunnan Province, The Second Affiliated Hospital of Dali University, 650011, Kunming, People's Republic of China. ., Pathogenic Organisms Department of Experimental Center, School of Basic Medical Sciences, Kunming Medical University, 650500, Kunming, People's Republic of China., Clinical Laboratory, The First People's Hospital of Yunnan Province, 650032, Kunming, People's Republic of China., Department of Geriatrics, The First People's Hospital of Yunnan Province, 650032, Kunming, People's Republic of China., Clinical Medicine College, Dali University, 671003, Dali, People's Republic of China., School of Pharmaceutical Sciences & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 650500, Kunming, People's Republic of China. .

Abstract:  Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes, such as free radical damage and cell apoptosis. This study aims to investigate whether microRNA-292-5p (miR-292-5p) protects against myocardial ischemia-reperfusion injury (IRI) via the peroxisome proliferator-activated receptor (PPAR)-α/-γ signaling pathway in myocardial IRI mice models. Mouse models of myocardial IRI were established. Adult male C57BL/6 mice were divided into different groups. The hemodynamic indexes, levels of related inflammatory factors and serum myocardial enzymes, and malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was applied to determine infarct size. TUNEL staining was used to detect cardiomyocyte apoptosis. RT-qPCR and western blotting were performed to measure the related gene expressions. Compared with the model group and the T0070907 + miR-292-5p inhibitor, the miR-292-5p inhibitor group exhibited decreased incidence and duration time of ventricular tachycardia and ventricular fibrillation, serum myocardial enzymes, TNF-α, IL-6, IL-1β, MDA, cardiomyocyte apoptosis, expressions of Bax and p53 in addition to increased SOD and GSH-Px activity, and increased expressions of Bcl-2, PPARα, PPARγ, PLIN5, AQP7, and PCK1. The T0070907 group exhibited opposite results compared to the miR-292-5p inhibitor group. The results indicate that miR-292-5p downregulation protects against myocardial IRI through activation of the PPAR-α/PPAR-γ signaling pathway. 

Retracted: No

PubPeer comments:
 Fig 8a.  Protein expression of related factors examined by western blotting . ![file] Colored rectangles are for comparison with Fig 9A from [Wu et al (2018a)] , and 5C of [Wu et al (2018b)] . ![] Fig. 3C from [Jaing et al (2018)] ; and 7C from [Lu et al (2018)] . ![] Other manifestations are linked in those threads. ,