Department of Geriatrics, Zhejiang Aged Care Hospital, Hangzhou Normal University, Hangzhou 310000, Zhejiang, China.
Zhejiang Institute for Food and Drug Control, Hangzhou 310012, Zhejiang, China.
Aging (Albany NY). 2023 Nov 20;15(22):13176-13193. doi: 10.18632/aging.205233.
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 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. 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.
本研究旨在通过生物信息学和实验验证，了解糖尿病肾病中受调控的细胞死亡（RCD）的机制，并鉴定相关的生物标志物。从公共数据库中获取了批量和单细胞 RNA 测序数据集，并使用与 RCD 相关的基因集（包括自噬、坏死性凋亡、细胞焦亡、细胞凋亡和铁死亡）进行基因集变异分析（GSVA）进行分析。使用加权基因相关网络分析（WGCNA）鉴定 RCD 相关基因生物标志物。通过独立队列的实验和实验进行验证。GSVA 显示糖尿病肾病中坏死性凋亡评分较高。鉴定出三种与坏死性凋亡相关的生物标志物 EGF、PAG1 和 ZFP36，它们对糖尿病肾病具有很强的诊断能力。实验表明，高糖处理的 HK-2 细胞中坏死性凋亡标志物水平较高。因此，生物信息学和实验验证鉴定出 EGF 和 PAG1 为糖尿病肾病的坏死性凋亡相关生物标志物。
