Identification and Validation of Potential Biomarkers and Their Functions in Acute Kidney Injury

Abstract

Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs, and the therapeutic measures are still limited. This study aims to investigate crucial genes correlated with AKI, and their potential functions, which might contribute to a better understanding of AKI pathogenesis. The highthroughput data GSE52004 and GSE98622 were downloaded from Gene Expression Omnibus; four group sets were extracted and integrated. Differentially expressed genes (DEGs) in the four group sets were identified by limma package in R software. The overlapping DEGs among four group sets were further analyzed by the VennDiagram package, and their potential functions were analyzed by the GO and KEGG pathway enrichment analyses using the DAVID database. Furthermore, the protein-protein interaction (PPI) network was constructed by STRING, and the functional modules of the PPI network were filtered by MCODE and ClusterOne in Cytoscape. Hub genes of overlapping DEGs were identified by Cyto-Hubba and cytoNCA. The expression of 35 key genes was validated by quantitative real-time PCR (qRT-PCR). Western blot and immunofluorescence were performed to validate an important gene Egr1. A total of 722 overlapping DEGs were differentially expressed in at least three group sets. These genes mainly enriched in cell proliferation and fibroblast proliferation. Additionally, 5 significant modules and 21 hub genes, such as Havcr1, Krt20, Sox9, Egr1, Timp1, Serpine1, Edn1, and Apln were screened by analyzing the PPI networks. The 5 significant modules were mainly enriched in complement and coagulation cascades and Metabolic pathways, and the top 21 hub genes were mainly enriched in positive regulation of cell proliferation. Through validation, Krt20 were identified as the top 1 upregulated genes with a log2 (fold change) larger than 10 in all these 35 genes, and 21 genes were validated as significantly upregulated; Egr1 was validated as an upregulated gene in AKI in both RNA and protein level. In conclusion, by integrated analysis of different high-throughput data and validation by experiment, several crucial genes were identified in AKI, such as Havcr1, Krt20, Sox9, Egr1, Timp1, Serpine1, Edn1, and Apln. These genes were very important in the process of AKI, which could be further utilized to explore novel diagnostic and therapeutic strategies.

No safe renal warm ischemia time—The molecular network characteristics and pathological features of mild to severe ischemia reperfusion kidney injury

“…Prostaglandin-endoperoxide synthase 2 (Ptgs2), also called cyclooxygenase-2(Cox-2), is positively correlated with the severity of the inflammatory response (Fan et al, 2021). Ptgs2 was reported upregulated after AKI in our previously research (Chen et al, 2020). Inhibition of Ptgs2 plays as a renal protective role against ischemia-induced damage in AKI (Fan et al, 2021;Liu et al, 2021).…”

Single Cell Dissection of Epithelial-Immune Cellular Interplay in Acute Kidney Injury Microenvironment

“…We then analyzed the transcription characteristic between PTC-new and normal PTCs, and explored the difference between the PTC-new and normal PTCs ( Figures 3A–D ). Interestingly, most up-regulated genes or transcription factors in PTC-new were kidney injury or repair regulated genes such as Klf4 ( 25 ), Klf6 ( 26 ), Neat1 ( 27 ), Malat1 ( 28 ), and Egr1 ( 29 ) ( Figures 3A – D ). Compared to normal PTCs, the PTC-new exhibited a high level of MAPK, TNF signaling pathway and associated genes Dusp1 and Jun ( Figure 3E ), which also supported the findings that PTC-new were pro-inflammatory.…”

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch–Schönlein Purpura Nephritis

“…SERPINE1, also known as plasminogen activator inhibitor type 1 (PAI-1), is produced in small amounts in healthy kidneys but is highly expressed in chronic kidney diseases [ 32 ]. SERPINE1 might be used as a potential biomarker for the pathology and progression of kidney diseases [ 33 ]. We found that SERPINE1 expression was regulated by HJ and GQZ.…”