Aging
Navigate
Submit an Article
Research Paper|Volume 15, Issue 22|pp 13176—13193

Investigating EGF and PAG1 as necroptosis-related biomarkers for diabetic nephropathy: an in silico and in vitro validation study

Yuejun Wang1, Linlin Zhang2, Zhiping Peng3
  • 1Department of Geriatrics, Zhejiang Aged Care Hospital, Hangzhou Normal University, Hangzhou 310000, Zhejiang, China
  • 2Zhejiang Institute for Food and Drug Control, Hangzhou 310012, Zhejiang, China
  • 3Department of Gerontology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang, China
Received: August 9, 2023Accepted: October 23, 2023Published: November 20, 2023
https://doi.org/10.18632/aging.205233

Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The current study aims to understand the mechanisms behind regulated cell death (RCD) in diabetic nephropathy and identify related biomarkers through bioinformatics and experimental validation. Datasets of bulk and single-cell RNA sequencing were obtained from public databases and analyzed using gene set variation analysis (GSVA) with gene sets related to RCD, including autophagy, necroptosis, pyroptosis, apoptosis, and ferroptosis. RCD-related gene biomarkers were identified using weighted gene correlation network analysis (WGCNA). The results were verified through experiments with an independent cohort and in vitro experiments. The GSVA revealed higher necroptosis scores in diabetic nephropathy. Three necroptosis-related biomarkers, EGF, PAG1, and ZFP36, were identified and showed strong diagnostic ability for diabetic kidney disease. In vitro experiments showed high levels of necroptotic markers in HK-2 cells treated with high glucose. Bioinformatics and experimental validation have thus identified EGF and PAG1 as necroptosis-related biomarkers for diabetic nephropathy.