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

Sun, Donglin1; Wei, Shuqi2; Wang, Dandan3; Zeng, Min4; Mo, Yihao4; Li, Huafeng4; Liang, Caixing4; Li, Lu5; Zhang, Jun Wei4; Wang, Li4

2024-01-08

10.3389/fimmu.2023.1328757

FRONTIERS IN IMMUNOLOGY   影响因子和分区

1664-3224

Introduction 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.Methods 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.Results and discussion 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.

glomeruli diabetic nephropathy cellular senescence molecular docking diagnostic marker therapeutic targets

SCI

英语

通讯

Shenzhen Fundamental Research Program[JCYJ20190808095615389]

Immunology

Immunology

WOS:001169128800001

FRONTIERS MEDIA SA

Web of Science

1.Southern Med Univ, Shenzhen Hosp, Dept Urol, Shenzhen, Peoples R China
2.Guangzhou Med Univ, Ctr Canc & Immunol Res, State Key Lab Resp Dis, Guangzhou, Peoples R China
3.Shenzhen Tradit Chinese Med Hosp, Dept Nephrol, Shenzhen, Guangdong, Peoples R China
4.Southern Med University, Affiliated Hosp, Shenzhen Longhua New Dist Peoples Hosp, Shenzhen, Peoples R China
5.Southern Univ Sci & Technol, Affiliated Hosp 2, Shenzhen, Peoples R China

Sun, Donglin,Wei, Shuqi,Wang, Dandan,et al. Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence[J]. FRONTIERS IN IMMUNOLOGY,2024,14.

Sun, Donglin.,Wei, Shuqi.,Wang, Dandan.,Zeng, Min.,Mo, Yihao.,...&Wang, Li.(2024).Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence.FRONTIERS IN IMMUNOLOGY,14.

Sun, Donglin,et al."Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence".FRONTIERS IN IMMUNOLOGY 14(2024).