Study of long non-coding RNA and mitochondrial dysfunction in diabetic rats

Abstract

Abstract Diabetes mellitus (DM) is a worldwide health problem. Many factors participate in the pathogenesis of DM, including genetic, autoimmune, metabolic, dietary and environmental factors. Intact mitochondrial function is essential for prompt cellular metabolism and energy balance. Malfunctioning mitochondria lead to disturbed glucose metabolism and therefore evolving of DM. Epigenetics plays a role in the control of geneencoded proteins of mitochondrial function and dynamics. One of the primary epigenetic effectors is a family of long non-coding RNAs. The role of lncRNA, H19 in the regulation of mitochondrial dynamics has been recently investigated. The Aim of the work This study aims to evaluate the possible functional role of lncRNA, H19 and its relation to mitofusin-2 (MFN2) expression in diabetic rats. Subjects and methods This study was performed on adult male albino rats divided into diabetic and control groups. Induction of type 1 DM was conducted through single intraperitoneal injection of streptozotocin. Serum measurement of glucose, lipid profile, urea, creatinine, and creatine kinase were performed. Blood pressure measurement, ECG recording, and echocardiography were also performed. Histological examination of cardiac and renal tissues was also performed. In addition, quantitative expression of cardiac and renal tissue MFN2 and lncRNA H19 was determined using qPCR. Results Serum CK-MB and lipid profile levels were markedly elevated in diabetic group compared to controls. Also, kidney functions (serum creatinine, creatinine clearance and albumin creatinine ratio) were markedly elevated in diabetic group compared to controls. Histological examination revealed necrotic changes and intercellular micro hemorrhages in both cardiac and renal tissues of diabetic rats. Expression level of MFN2 gene was lower in diabetic heart and significantly lower in diabetic kidney, as compared to control. Expression of lncRNA H19 was higher in diabetic heart and diabetic kidney as compared to control but without statistical significance. Conclusion In diabetic rats, hyperglycemia had inverse relationship with mitofusin expression and direct proportional relationship with H19 expression. We concluded that hyperglycemia has effect on mitochondrial dynamics suppressing fusion in favor of fission and mitophagy, while H19 expression serve to counterpart the effect of hyperglycemia. In the future, MFN and H19 could serve as potential therapeutic target to reverse effects of hyperglycemia and its complications in DM.