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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Systems Immunology
Volume 14 - 2023 | doi: 10.3389/fimmu.2023.1328757
This article is part of the Research Topic

Targeting Senescence-Associated Molecular Alterations to Treat Inflammatory Diseases

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Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence

Donglin Sun1 Shuqi Wei2 Dandan Wang3 Min Zeng4 Yihao Mo4 Huafeng Li4 Caixing Liang4 Lu Li5* Jun Wei Zhang4* Li Wang4*
  • 1Shenzhen Hospital, Southern Medical University, China
  • 2Guangzhou Medical University, China
  • 3Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, China
  • 4Nephrology Department, Shenzhen Longhua People's Hospital, China
  • 5Second Affiliated Hospital of Southern University of Science and Technology, China

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Diabetic nephropathy (DN), distinguished by detrimental changes in the renal glomeruli, is regarded as the leading cause of death from end-stage renal disease among diabetics. Cellular senescence plays a paramount role, profoundly affecting the onset and progression of chronic kidney disease (CKD) and acute kidney injuries. This study was designed to delve deeply into the pathological mechanisms between glomerulus-associated DN and cellular senescence.Glomerulus-associated DN datasets and cellular senescence-related genes were acquired from the Gene Expression Omnibus (GEO) and CellAge database respectively. By integrating bioinformatics and machine learning methodologies including the LASSO regression analysis and Random Forest, we screened out four signature genes. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of the selected genes. Rigorous experimental validations were subsequently conducted in the mouse model to corroborate the identification of three signature genes, namely LOX, FOXD1 and GJA1. Molecular docking with chlorogenic acids (CGA) was further established not only to validate LOX, FOXD1 and GJA1 as diagnostic markers but also reveal their potential therapeutic effects. In conclusion, our findings pinpointed three diagnostic markers of glomerulus-associated DN on the basis of cellular senescence.These markers could not only predict an increased risk of DN progression but also present promising therapeutic targets, potentially ushering in innovative treatments for DN in the elderly population.

Keywords: glomeruli, diabetic nephropathy, cellular senescence, molecular docking, Diagnostic marker, therapeutic targets

Received: 27 Oct 2023; Accepted: 14 Dec 2023.

Copyright: © 2023 Sun, Wei, Wang, Zeng, Mo, Li, Liang, Li, Zhang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Lu Li, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
Mx. Jun Wei Zhang, Nephrology Department, Shenzhen Longhua People's Hospital, Shenzhen, 518109, China
Prof. Li Wang, Nephrology Department, Shenzhen Longhua People's Hospital, Shenzhen, 518109, China