The Expressions Of Pigment Epithelium-derived Factor And Adipose Triglyceride Lipase In Human Kidney And Correlation With Renal Lipid Accumulation

As one of the most severe complications of diabetes worldwide,diabetic nephropathy(DN)is the leading cause of end stage kidney disease.Studies have shown that renal lipid accumulation plays an important role in the pathogenesis of diabetic nephropathy.In animal and cell culture models of diabetes,PEDF plays a protective role in the development and progression of DN,PEDF is thought to exert its biologic actions by binding to a cell surface receptor.As the first identified receptor for PEDF,ATGL was revealed to have specific binding affinity for PEDF and activate its enzymatic lipase property by binding PEDF.Here,our study is the first to show the co-localization of PEDF and ATGL in human kidney on protein and tissue level.PEDF and ATGL were significantly lower in human diabetic kidney.Simultaneously renal lipid accumulation was increased as compared to healthy kidney.Therefore,we suggest a role for PEDF in the regulation of renal lipid metabolism via ATGL and propose PEDF-ATGL nexus may as a possible therapeutic target in Diabetic nephropathy.Objective To evaluate whether pigment epithelium-derived factor plays roles in the regulation of renal lipid metabolism via adipose triglyceride lipase and to prevent the development of diabetic nephropathy.Methods The study was approved by the Medical Ethical Committee of Remin Hospital of Wuhan University Research Project.All subjects were provided their informed consent.Kidney samples were obtained from non-affected parts of tumor nephrectomy biopsies of patients with DM(n = 20)as a test group or patients without DM(n = 10)as a control group from the Department of Urology of Renmin Hospital of Wuhan University.Kidney tissue was stored at-80 ℃ for protein isolation or embedded in paraffin for periodic acid-schiff,double immunofluorescence staining.The other part kidney biopsy tissue was immediately fixed in Karnovsky’s fixative and then 1%buffered osmium tetroxide(method that preserved lipids)for Oil red O staining.Results Our study is the first to show co-localization of PEDF and ATGL in human kidney on protein and tissue level.PEDF and ATGL were significantly lower in human diabetes kidney,simultaneously renal lipid accumulation increased as compared to normal kidney.Conclusion Therefore,we suggest a role for PEDF in the regulation of renal lipid metabolism via ATGL and propose PEDF-ATGL nexus may as a possible therapeutic target in diabetic nephropathy.