Identification and Validation of Glomeruli Cellular Senescence‐Related Genes in Diabetic Nephropathy by Multiomics

Author:

Tang Chunyin12ORCID,Yang Chunsong1,Wang Peiwen2,Li Luxin2ORCID,Lin Yunzhu1,Yi Qiusha1,Tang Fengru1,Liu Lantao3,Zhou Wei1,Liu Dongwen1,Zhang Lingli1,Yuan Xiaohuan2ORCID

Affiliation:

1. Evidence‐Based Pharmacy Center Key Laboratory of Birth Defects and Related Diseases of Women and Children Department of Pharmacy West China Second University Hospital Sichuan University Chengdu 610000 China

2. College of Life Science Mudanjiang Medical University Mudanjiang 157000 China

3. Postgraduate Department Mudanjiang Medical University Mudanjiang 157011 China

Abstract

AbstractAccumulating evidence indicates that cellular premature senescence of the glomerulus, including endothelial cells, mesangial cells, and podocytes leads to diabetic nephropathy (DN), and DN is regarded as a clinical model of premature senescence. However, the role of cellular senescence‐associated genes in the glomerulus in DN progression remains unclear. Therefore, this work aims to identify and validate potential cellular aging‐related genes in the glomerulus in DN to provide novel clues for DN treatment based on anti‐aging. The microarray GSE96804 dataset, including 41 diabetic glomeruli and 20 control glomeruli, is retrieved from the Gene Expression Omnibus (GEO) database and cellular senescence‐related genes (CSRGs) are obtained from the GeneCards database and literature reports. Subsequently, PPI, GO, and KEGG enrichment are analyzed by screening the intersection between differentially expressed genes (DEGs) and CSRGs. scRNA‐seq dataset GSE127235 is used to verify core genes expression in glomerulocytes of mice. Finally, db/db mice are utilized to validate the hub gene expression in the glomeruli, and high glucose‐induced mesangial cells are used to confirm key gene expression. This study reveals that FOS and ZFP36 may play an anti‐aging role in DN to ameliorate cell intracellular premature aging in mesangial cells of glomeruli.

Publisher

Wiley

Subject

General Medicine

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