O-GlcNAcylation and Angiopoietin-like 4 (ANGPTL4) play critical roles in the onset and progression of diabetic nephropathy by modulating cellular signaling, lipid metabolism, and oxidative stress.
Diabetic nephropathy (DN) is a chronic renal complication characterized by persistent proteinuria, glomerular hypertrophy, impaired filtration capacity, and progressive renal fibrosis, ultimately leading to a gradual decline in kidney function. DN remains one of the leading causes of end-stage renal disease worldwide, contributing substantially to morbidity and mortality. Although the precise etiology of DN is not fully elucidated, its development is closely linked to prolonged hyperglycemia, renal hyperfiltration, accumulation of advanced glycation end products (AGEs), activation of pro-inflammatory cytokines, and oxidative stress-mediated injury. These pathogenic events involve multiple diabetes-associated pathways, including protein kinase C activation and increased reactive oxygen species (ROS) generation. O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a dynamic post-translational protein modification that is significantly upregulated in DN and plays a critical role in regulating cellular signaling pathways associated with disease initiation and progression. This review summarizes current evidence on the role of O-GlcNAcylation in modulating molecular mechanisms underlying DN. Furthermore, Angiopoietin-like 4 (ANGPTL4) has emerged as a key regulator of lipid metabolism through inhibition of lipoprotein lipase and interactions with integrins, influencing vascular permeability, oxidative stress, and tissue remodeling. Increasing evidence suggests that ANGPTL4 plays a pivotal role in DN onset and progression.
Pandey et al. (Sat,) conducted a review in Diabetic nephropathy. O-GlcNAcylation and ANGPTL4 was evaluated. O-GlcNAcylation and Angiopoietin-like 4 (ANGPTL4) play critical roles in the onset and progression of diabetic nephropathy by modulating cellular signaling, lipid metabolism, and oxidative stress.