The Alterations Of PGC-1α Expression And Epigenetic Modifications In The Retina Of Streptozotocin-induced Diabetic Rats

PURPOSE Diabetic retinopathy(DR)is a common microvascular complication of diabetes.The durable effect on complications of prior metabolic control is named metabolic memory.The purpose of this study is to investigate the role of epigenetic regulations of peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α)in the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression after hyperglycemia is terminated by detecting the expression levels PGC-1α and DNA methylation in the promoter region of PPARGC1A.METHODS Eighty rats were randomly divided into 4 groups,1.Control group(Con);2.Poor glycemic control group(PC),streptozotocin induced diabetic rats were maintained in poor glycemic control for 4 months;3.Poor glycemic control-good glycemic control group(PC-Rev),streptozotocin induced diabetic rats were allowed to maintain poor glycemic control for 2 months,followed by good glycemic control for 2 additional months;4.Good glycemic control group(GC),streptozotocin induced diabetic rats were maintained in good glycemic control for 4 months.The retinal tissues of rats were isolated,mRNA expression of PGC-1α and superoxide dismutase2(SOD2)were measured by real-time PCR(RT-PCR),protein expression of PGC-1αand manganese superoxide dismutase(MnSOD)were measured by western blot,DNA methylation in the promotor region of PPARGC1A were measured by bisulfite sequencing.RESULTS PGC-1α mRNA expression level in the retina of GC group,PC-Rev group and PC group decreased.The statistical difference was not found between the PC-Rev group and the PC group.The statistical difference was found between the GC group and the PC group.SOD2 mRNA expression level in the retina of GC group,PC-Rev group and PC group increased.PGC-1α and MnSOD protein expression levels decreased and the PC-Rev group had the similar alterations of PC group.Diabetes increased DNA methylation in the promotor region of of PPARGC1A gene of retina.The statistical difference was not found between the PC-Rev group and the PC group.CONCLUSIONS PGC-1α mRNA and protein expression levels in the retina of streptozotocin induced diabetic rats decreased,SOD2 mRNA expression level in the retina of diabetic rats increased,MnSOD protein expression level in the retina of diabetic rats decreased,these changes had metabolic memory characteristics.Increased DNA methylation in the promotor region of of PPARGC1A when exposed to high glucose may has a role in the regulation of PGC-1α expression and metabolic memory.