Species-Specific Renal Localization of O-GlcNAc Transferase and Its Alteration in CKD

Background: Protein glycosylation patterns vary across species and cell types, influencing protein function. O-linked N-acetylglucosamine (O-GlcNAc) is a cytoplasmic and nuclear modification catalyzed by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). While altered OGT expression is implicated in chronic kidney disease (CKD), its renal localization remains poorly understood. We investigated OGT localization in various species with normal or CKD conditions. Methods: Kidneys from humans (healthy, n = 3; CKD, n = 4), dogs (healthy and CKD, n = 4 each), cats (healthy, n = 4; CKD, n = 2), and C57BL/6N mice (healthy and CKD induced by unilateral ureteral obstruction (UUO), n = 4 each) were histopathologically examined. Immunohistochemistry for OGT, O-GlcNAc, OGA, renin, and α-smooth muscle actin (α-SMA) was performed. In human kidneys, OGT-positive (+) cortical area was quantified. Results: OGT localized to podocytes and renal tubular epithelial cells in kidneys of all examined species with healthy condition. In dogs and cats with CKD, OGT was concentrated on the apical side of proximal tubular cells, whereas no significant change in OGT localization was noted in UUO mice. Importantly, human kidneys exhibited a unique pattern: granular OGT+reaction was co-localized with that of renin in juxtaglomerular cells. In CKD cases, OGT+renin+granules extended beyond juxtaglomerular cells into α-SMA-negative smooth muscle cells of the afferent arterioles. Quantitative values of cortical OGT+reactions tended to be higher in CKD patients than in healthy individuals (0.08%±0.040 vs. 0.04%±0.006). These OGT+/renin+cells expressed low OGA and lacked detectable O-GlcNAc. Conclusion: OGT localization differs among species and pathological states. In humans, granular OGT in renin+cells of the afferent arterioles represents a CKD-associated, species-specific feature. The absence of human O-GlcNAc in OGT+/renin+cells suggests either rapid O-GlcNAc turnover or novel OGT functions in renin processing or secretion. These findings potentially highlight a unique role for OGT in human renin-producing cells. Further studies are needed to clarify the physiological role of OGT, as well as its pathological and clinical significance in human CKD.