Authors: Geng Shuang, Chen Youxin, Yao Xiang, Xu Haiyan, Zhang Gumuyang, Xia Song, Liu Ziyang
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Objective
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 after hyperglycemia was terminated.
Methods
Diabetic rat model was established by intraperitoneal injection of streptozotocin (STZ). Sixty diabetic rats were randomly divided into 3 groups, poor glycemic control group rats were maintained in poor glycemic control for 4 months; semi glycemic control group rats were maintained in poor glycemic control for 2 months, followed by good glycemic control for 2 additional months; good glycemic control group rats were maintained in good glycemic control for 4 months.Twenty normal rats served as control group.The mRNA expression of PGC-1α and superoxide dismutase 2 (SOD2) of retina were measured by real-time PCR; the expression of PGC-1α and manganese superoxide dismutase (MnSOD) protein were measured by Western blot; the situation of DNA methylation in the promotor region of PPARGC1A was measured by bisulfite sequencing.
Results
The body-weight in the control group was significantly higher than that in the poor glycemic control group, semi glycemic control group and good glycemic control group (all at P=0.000). The blood glucose value in the poor glycemic control group was significantly higher than that in the control group (P=0.000). The expression levels of PGC-1α mRNA were significantly lower and the expression levels of SOD2 mRNA were significantly higher in the good glycemic control group, semi glycemic control group and poor glycemic control group than those in the control group (all at P<0.05). The expression levels of PGC-1α and SOD2 mRNA were significantly different between the good glycemic control group and poor glycemic control group (both at P<0.05). Compared with the control group, the expression levels of PGC-1α and MnSOD protein were decreased in the diabetic model groups, with significant differences between them (all at P<0.05). The expression level of PGC-1α protein was significantly higher in the good glycemic control group than that in the poor glycemic control group (P<0.05). Diabetes increased DNA methylation in the promotor region of PPARGC1A gene of retina.The DNA methylation level was significantly higher in the poor glycemic control group and semi glycemic control group than that in the control group (P=0.008, 0.031). No statistical difference was found between the poor glycemic control group and semi glycemic control group (P>0.05).
Conclusions
The expressions of PGC-1α mRNA and protein and MnSOD protein in the retina of STZ induced diabetic rats are decreased, the expression of SOD2 mRNA is increased, the expression changes have metabolic memory characteristics.Increased DNA methylation in the promotor region of PPARGC1A when exposed to high glucose may have a role in the regulation of PGC-1α expression and metabolic memory.