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

IF 11.4 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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引用次数: 0

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.

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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.