Liu Minghui, Yang Wenwen, Qu Shuang, Zhao Tingting, Jiang Song, Peng Suming, Zhang Mingchao, Xuan Ji, Liu Zhihong, Zen Ke
School of Pharmaceutical Science, Nanjing Tech University, 30 South Puzhu Road, Nanjing, Jiangsu 211816, China; State Key Laboratory of Pharmaceutical Biotechnology, Department of Gastroenterology, Drum Tower Hospital, Nanjing University, School of Life Sciences, Nanjing, Jiangsu 210093, China.
State Key Laboratory of Pharmaceutical Biotechnology, Department of Gastroenterology, Drum Tower Hospital, Nanjing University, School of Life Sciences, Nanjing, Jiangsu 210093, China.
J Adv Res. 2024 Dec 24. doi: 10.1016/j.jare.2024.12.027.
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.
糖尿病肾病（DN）发病机制复杂多样，是终末期肾病（ESRD）的首要诱因。本研究旨在分析肾小球醛缩酶B（ALDOB）在DN进展中的水平及非代谢作用。
分别对50例DN患者和25例对照者进行肾小球蛋白质组学和转录组分析。采用人肾活检、培养的足细胞和小鼠模型研究ALDOB水平及功能。
在受DN影响的肾小球以及暴露于炎性细胞因子的人和小鼠足细胞中，ALDOB均显著下调。ALDOB减少会增加足细胞损伤，而腺病毒介导的ALDOB过表达可显著减轻糖尿病小鼠模型的肾损伤。从机制上讲，ALDOB减少会触发足细胞内的Akt/GSK/β-连环蛋白信号级联反应。
我们的研究结果揭示了肾小球ALDOB在预防足细胞损伤和肾纤维化方面的一种新的非代谢作用。
