Related Experiment Video
Updated: Jul 22, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy
Meng Yan1,2, Wenwen Li3, Rui Wei3
1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. yanmeng0727@xzhmu.edu.cn.
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.
Insights
Researchers identified two diabetic nephropathy (DN) subtypes linked to inflammation and metabolism. They also found 65 potential drugs targeting key pyroptosis-related genes for DN treatment.
Area of Science:
- Nephrology
- Immunology
- Genetics
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM).
- Inflammation plays a key role in DN development.
- Pyroptosis, a form of programmed cell death, is linked to immune inflammation and may offer novel therapeutic targets for DN.
Purpose of the Study:
- To identify pyroptosis-related genes in DN.
- To develop a predictive model for DN based on pyroptosis genes.
- To discover potential therapeutic drugs for DN targeting these genes.
Main Methods:
- Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets (GSE96804, GSE30528, GSE142025) to identify differentially expressed pyroptosis-related genes.
- Least Absolute Shrinkage and Selection Operator (LASSO) regression for predictive model construction.
- Consensus clustering, Gene Set Variation Analysis (GSVA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analysis to identify subtypes, pathways, and hub genes.
- Drug-Gene Interaction Database (DGIdb) for drug screening.
Main Results:
- Identified 24 differentially expressed pyroptosis-related genes in DN.
- Developed a 16-gene predictive model using LASSO regression.
- Classified DN into two subtypes based on gene expression, associated with inflammation, immune response, and cell metabolism.
- Identified 10 hub genes and predicted 65 potential therapeutic compounds targeting these genes.
Conclusions:
- Two distinct pyroptosis-related DN subtypes were identified.
- 65 potential therapeutic agents/compounds targeting key genes were predicted.
- These findings may offer new therapeutic strategies for diabetic nephropathy.
More Related Videos
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
07:15Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
