Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy

Meng Yan; Wenwen Li; Rui Wei; Shuwen Li; Yan Liu; Yuqian Huang; Yunye Zhang; Zihao Lu; Qian Lu

doi:10.1186/s12967-023-04350-w

Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy

J Transl Med. 2023 Jul 21;21(1):490. doi: 10.1186/s12967-023-04350-w.

Authors

Meng Yan^#^{1

2}, Wenwen Li^#³, Rui Wei³, Shuwen Li³, Yan Liu^{4

5}, Yuqian Huang³, Yunye Zhang³, Zihao Lu³, Qian Lu^{6

7}

Affiliations

¹ Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. yanmeng0727@xzhmu.edu.cn.
² Department of Clinical Pharmacology, School of Pharmacy, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China. yanmeng0727@xzhmu.edu.cn.
³ Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
⁴ Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, China.
⁵ Key Laboratory of Genetic Foundation and Clinical Application, Department of Genetics, Xuzhou Engineering Research Center of Medical Genetics and Transformation, Xuzhou Medical University, Xuzhou, China.
⁶ Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. luqian@xzhmu.edu.cn.
⁷ Department of Clinical Pharmacology, School of Pharmacy, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China. luqian@xzhmu.edu.cn.

^# Contributed equally.

Abstract

Background: Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN.

Methods: DN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein-protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes.

Results: A total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes.

Conclusion: We identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.

Keywords: Diabetic nephropathy; Drug–gene prediction; Enrichment analysis; Lasso regression; Pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Cluster Analysis
Computational Biology
Diabetes Mellitus*
Diabetic Nephropathies* / drug therapy
Diabetic Nephropathies* / genetics
Humans
Inflammation
Pyroptosis / genetics