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

IF 13 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of Advanced Research Pub Date : 2024-12-24 DOI:10.1016/j.jare.2024.12.027

Minghui Liu, Wenwen Yang, Shuang Qu, Tingting Zhao, Song Jiang, Suming Peng, Mingchao Zhang, Ji Xuan, Zhihong Liu, Ke Zen

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Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

Our findings reveal a novel non-metabolic role of glomerular ALDOB in protecting against podocyte injury and renal fibrosis.

Abstract Image

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糖尿病肾病患者肾小球醛缩酶B的缺失通过激活Akt/GSK/β-连环蛋白轴促进肾纤维化

目的糖尿病肾病（DN）是终末期肾病（ESRD）最重要的催化剂，其发病机制复杂且多面性。本研究旨在分析肾小球醛缩酶B （glomer小球醛缩酶B， ALDOB）在肾病进展中的水平及其非代谢作用。方法对50例DN患者和25例对照组进行肾小球蛋白质组学和转录组学分析。采用人肾活检、培养足细胞和小鼠模型研究ALDOB水平和功能。结果在dn影响的肾小球以及暴露于炎性细胞因子的人和鼠足细胞中，saldob被强烈下调。在糖尿病小鼠模型中，ALDOB减少会增加足细胞损伤，而腺病毒介导的ALDOB过表达会显著减轻肾损伤。在机制上，ALDOB的减少触发足细胞内Akt/GSK/β-catenin信号级联。结论肾小球ALDOB在防止足细胞损伤和肾纤维化方面具有新的非代谢作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Advanced Research Multidisciplinary-Multidisciplinary

CiteScore

21.60

自引率

0.90%

发文量

280

审稿时长

12 weeks

期刊介绍： Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.

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