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Updated: Aug 15, 2025

Using 2-Photon Microscopy to Quantify the Effects of Chronic Unilateral Ureteral Obstruction on Glomerular Processes
Published on: March 4, 2022
Identification of Hub Genes Correlated with the Initiation and Development in Chronic Kidney Disease via
Kai Zhu1,2, Xinxin Li3, Likun Gao4
1Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China, 13484200@qq.com.
Introduction:
Chronic kidney disease (CKD) is a major public health issue worldwide, which is characterized by irreversible loss of nephron and renal function. However, the molecular mechanism of CKD remains underexplored.
Methods:
This study integrated three transcriptional profile datasets to investigate the molecular mechanism of CKD. The differentially expressed genes (DEGs) between Sham control (Con) and unilateral ureteral obstruction (UUO)-operated mice were analyzed by utilizing the limma package in R. The shared DEGs were analyzed by Gene Ontology and functional enrichment. Protein-protein interactions (PPIs) were constructed by utilizing the STRING database. Hub genes were analyzed by MCODE and Cytohubba. We further validated the gene expression by using the other dataset and mouse UUO model.
Results:
A total of 315 shared DEGs between Con and UUO samples were identified. Gene function and KEGG pathway enrichment revealed that DEGs were mainly enriched in inflammatory response, immune system process, and chemokine signaling pathway. Two modules were clustered based on PPI network analysis. Module 1 contained 13 genes related to macrophage activation, migration, and chemotaxis. Ten hub genes were identified by PPI network analysis. Subsequently, the expression levels of hub genes were validated with the other dataset. Finally, these four validated hub genes were further confirmed by our UUO mice. Three validated hub genes, Gng2, Pf4, and Ccl9, showed significant response to UUO.
Conclusion:
Our study reveals the coordination of genes during UUO and provides a promising gene panel for CKD treatment. GNG2 and PF4 were identified as potential targets for developing CKD drugs.
Insights
This study investigated the molecular mechanisms of chronic kidney disease (CKD) using gene expression analysis in mice. Key genes like GNG2 and PF4 were identified as potential therapeutic targets for CKD treatment.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Chronic kidney disease (CKD) presents a significant global health challenge, marked by irreversible nephron loss and declining renal function.
- The intricate molecular pathways driving CKD progression remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying CKD.
- To identify key genes and pathways involved in the pathogenesis of CKD.
Main Methods:
- Integrated three transcriptional profile datasets to identify differentially expressed genes (DEGs) in a mouse model of unilateral ureteral obstruction (UUO).
- Utilized bioinformatics tools including limma, Gene Ontology, KEGG pathway analysis, STRING database, MCODE, and Cytohubba for gene and protein-protein interaction network analysis.
- Validated gene expression changes in an independent dataset and a mouse UUO model.
Main Results:
- Identified 315 shared DEGs between control and UUO samples, enriched in inflammatory response, immune processes, and chemokine signaling.
- Protein-protein interaction network analysis revealed modules related to macrophage activation and identified ten hub genes.
- Validated four hub genes, with GNG2, PF4, and CCL9 showing significant response to UUO.
Conclusions:
- The study highlights coordinated gene expression during UUO, offering a potential gene panel for CKD therapeutic strategies.
- GNG2 and PF4 emerge as promising molecular targets for the development of novel CKD therapeutics.
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