Evidence of O-linked N-acetylglucosamine in diabetic nephropathy

Abstract Aims There is increasing evidence that O- linked N -acetylglucosamine ( O -GlcNAc) plays an important role in cell signaling pathways. It has also been reported that increases in O -GlcNAc contribute to the development of diabetes and diabetic complications; however, little is known about O -GlcNAc levels in diabetic nephropathy (DNP). Therefore the goal of this study was to determine whether O -GlcNAc could be detected in human kidney biopsy specimens, and if so to examine whether O -GlcNAc levels were increased in the kidneys of patients with DNP compared to the non-diabetic individuals. Main methods Kidney biopsy specimens were obtained from type-2 diabetic patients ( n  = 6) and patients diagnosed with thin basement membrane nephropathy ( n  = 7) were used as non-diabetic controls. O -GlcNAc levels were assessed by immunohistochemistry using the anti- O -GlcNAc antibody CTD110.6. Key findings We show that O -GlcNAc modification of proteins can be detected in the human kidney biopsy specimens. Furthermore, in diabetic patients, we found significantly increased numbers of O -GlcNAc positive cells in the glomeruli and significantly elevated staining in the tubuli (both in the nucleus and in the cytosol). In addition we also observed an intense, granular O -GlcNAc staining specifically in diabetic tubuli. Significance In light of the increase in O -GlcNAc staining in the diabetic patients, we propose that increased O -GlcNAc levels might contribute to the development of diabetic nephropathy.