# Identification of Hub Genes Correlated with the Initiation and Progression of CKD in the Unilateral Ureteral Obstruction Model

**Authors:** Xinxin Li, Junjie Li, Xiaobing Yao, Jun Yang

PMC · DOI: 10.3390/biomedicines13061316 · Biomedicines · 2025-05-27

## TL;DR

This study identifies key genes linked to the start and progression of chronic kidney disease using mouse models and gene expression data.

## Contribution

The study discovers four hub genes (Fgg, Penk, Ckap4, Gpc3) as potential therapeutic targets for chronic kidney disease.

## Key findings

- 381 differentially expressed genes were identified between control and UUO mice.
- Nine hub genes were validated using dataset GSE118339 and in vivo experiments.
- DEGs were primarily associated with inflammation and fibrosis processes.

## Abstract

Background: Chronic kidney disease (CKD) is a global health problem marked by a persistent deterioration in the function of the nephrons and kidneys. To identify novel therapies for CKD, we investigated the molecular targets associated with the initiation and progression of the disease. Methods: The transcriptional profile dataset of GSE42303 was downloaded from GEO (The Gene Expression Omnibus). Utilizing the R package limma, the differentially expressed genes (DEGs) were identified between control (Con) and unilateral ureteral obstruction (UUO) mice. Then, functional enrichment, protein–protein interactions (PPI) and subsequent hub genes were identified by multiple bioinformatics approaches. Further validations of these hub genes were confirmed through the GSE118339 dataset and in vivo experiments. Results: We found 381 DEGs between Con and UUO mice (308 up-regulated genes and 73 down-regulated genes). GO functions and pathway analysis indicated that DEGs were mainly enriched in activities associated with inflammation and fibrosis. The mRNA expressions of nine hub genes were identified and confirmed by dataset GSE118339 and in vivo experiments. Conclusions: The hub genes Fgg, Penk, Ckap4, and Gpc3 may be new prospective targets for the treatment of the initiation and progression of CKD.

## Linked entities

- **Genes:** FGG (fibrinogen gamma chain) [NCBI Gene 2266], PENK (proenkephalin) [NCBI Gene 5179], CKAP4 (cytoskeleton associated protein 4) [NCBI Gene 10970], GPC3 (glypican 3) [NCBI Gene 2719]
- **Diseases:** chronic kidney disease (MONDO:0005300)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Gpc3 (glypican 3) [NCBI Gene 14734] {aka OCI-5}, Ckap4 (cytoskeleton-associated protein 4) [NCBI Gene 216197] {aka 5630400A09Rik, CLIMP-63, P63}, Fgg (fibrinogen gamma chain) [NCBI Gene 99571] {aka 3010002H13Rik}, Penk (preproenkephalin) [NCBI Gene 18619] {aka ENK, PPA, Penk1}
- **Diseases:** UUO (MESH:D014517), CKD (MESH:D051436), inflammation (MESH:D007249), fibrosis (MESH:D005355)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12189713/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12189713/full.md

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Source: https://tomesphere.com/paper/PMC12189713