Work

Loss of glomerular aldolase B in diabetic nephropathy promotes renal fibrosis via activating Akt/GSK/β-catenin axis

Year: 2024

Type: article

Abstract: • Aldolase B is the most downregulated gene in diabetic nephropathy glomeruli at both protein and mRNA level. • Diabetic nephropathy-associated inflammatory cytokines decrease podocyte aldolase B level. • Aldolase B reduction triggers the Akt/GSK/β-catenin signaling cascade, leading to podocyte injury. Diabetic nephropathy (DN), characterized by a complex and multifaceted pathogenesis, stands as the foremost catalyst behind end-stage renal disease (ESRD). This study aims to analyze the level and non-metabolic role of glomerular aldolase B (ALDOB) in DN progression. Glomerular proteomics and transcriptome are analyzed from 50 DN patients and 25 controls, respectively. Human kidney biopsy, cultured podocytes and mouse models are employed to study ALDOB levels and function. ALDOB is strongly downregulated in DN-affected glomeruli, as well as in human and murine podocytes exposed to inflammatory cytokines. ALDOB reduction increases podocyte injury, while adenovirus-mediated ALDOB overexpression leads to substantial alleviation of renal injuries in a diabetic mouse model. Mechanistically, ALDOB reduction triggers the Akt/GSK/β-catenin signaling cascade within podocytes. Our findings reveal a novel non-metabolic role of glomerular ALDOB in protecting against podocyte injury and renal fibrosis.

Source: Journal of Advanced Research

DOI: 10.1016/j.jare.2024.12.027