Identification of Hub Genes Associated with the Development of Acute Kidney Injury by Weighted Gene Co-Expression Network Analysis

Abstract

<b><i>Background:</i></b> Acute kidney injury (AKI) is a severe clinical syndrome, causing a profound medical and socioeconomic burden worldwide. This study aimed to explore underlying molecular targets related to the progression of AKI. <b><i>Methods:</i></b> A public database originated from the NCBI GEO database (serial number: GSE121190) and a well-established and unbiased method of weighted gene co-expression network analysis (WGCNA) to identify hub genes and potential pathways were used. Furthermore, the unbiased hub genes were validated in 2 classic models of AKI in a rodent model: chemically established AKI by cisplatin- and ischemia reperfusion-induced AKI. <b><i>Results:</i></b> A total of 17 modules were finally obtained by the unbiased method of WGCNA, where the genes in turquoise module displayed strong correlation with the development of AKI. In addition, the results of gene ontology revealed that the genes in turquoise module were involved in renal injury and renal fibrosis. Thus, the hub genes were further validated by experimental methods and primarily obtained Rplp1 and Lgals1 as key candidate genes related to the progression of AKI by the advantage of quantitative PCR, Western blotting, and in situ tissue fluorescence. Importantly, the expression of Rplp1 and Lgals1 at the protein level showed positive correlation with renal function, including serum Cr and BUN. <b><i>Conclusions:</i></b> By the advantage of unbiased bioinformatic method and consequent experimental verification, this study lays the foundation basis for the pathogenesis and therapeutic agent development of AKI.

Establishment of Multiple Parameter Reference Intervals for Different Age Groups in Qingdao, China

“…Some studies have shown that the increase of FBG levels is an important stage that directly or indirectly leads to the occurrence and death of cardiovascular events [ 8 ]. AST, ALT, BUN, Cr, and so on are among the most commonly used indexes for detecting liver and renal function in clinics [ 9 , 10 ]. The levels of AST, ALT, BUN, and Cr increased obviously when the liver and kidney were damaged.…”

Comprehensive analysis of fifteen hub genes to identify a promising diagnostic model, regulated networks, and immune cell infiltration in acute kidney injury

“…Clinically significant modules were identified by calculating the correlation between ME and clinical trait, and the degree of connection was measured. Gene significance (GS) was used to evaluate this degree and a higher GS indicated the increased significance of genes 10–12 …”

“…Gene significance (GS) was used to evaluate this degree and a higher GS indicated the increased significance of genes. 10 , 11 , 12 …”

“…Gene significance (GS) was used to evaluate this degree and a higher GS indicated the increased significance of genes. [10][11][12] 2.4 | Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis GO and KEGG pathway enrichment analyses were performed using an online database by DAVID 6.8 (https://david.ncifc rf.gov/). GO and KEGG pathway enrichment analysis was used to identify potential biological mechanism of genes.…”

Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice

“…Recent multiple experimental analyses indicated that Rplp1 significantly upregulated display dramatically increased in the kidneys of Cis-AKI and display dramatically increased after 3 days and decreased after 7 days ( Lin et al, 2021 ). Moreover, a previous study focused on the relationship between the expression of TIMP1 and the incidence of sepsis-associated acute kidney injury (SAAKI).…”