Identification of hub genes in CKD

What is it about?

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 under explored. This study integrated three transcriptional profile datasets GSE38117, GSE87212, and GSE125015 to investigate the molecular mechanism of CKD. The differentially expressed genes (DEGs) between 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 (GO) and functional enrichment. Protein-protein interactions (PPI) were constructed by utilizing the STRING database. Hub genes were analyzed by MCODE and Cytohubba. We further validated the gene expression by using the dataset GSE121190 and mice UUO model. A total of 315 shared DEGs (272 up- and 43 down-regulated genes) 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, innate immune response 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 (Gng2, Ccl6, Ccl9, Anxa1, Lpar3, Pf4, C3ar1, Sucnr1, Gpsm3 and Gpr18) were identified by PPI network analysis. Subsequently, the expression levels of hub genes were validated with the dataset GSE121190. 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. Our study reveals the coordination of genes during UUO, and provides a promising gene panel CKD treatment. Gng2 and Pf4 were identified as potential targets for developing CKD drugs.

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Why is it important?

In this manuscript, we analyzed gene expression profile data of Unilateral ureteral obstruction (UUO) using bioinformatic methods. Gng2 and Pf4 were identified, and validated for the first time, which may be potential targets or biomarkers for diagnosing or treating the development of CKD.