Identification of VCAN as Hub Gene for Diabetic Kidney Disease Immune Injury Using Integrated Bioinformatics Analysis

Qiannan Xu; Qiannan Xu; Qiannan Xu; Binjue Li; Binjue Li; Binjue Li; Yucheng Wang; Yucheng Wang; Yucheng Wang; Cuili Wang; Cuili Wang; Cuili Wang; Shi Feng; Shi Feng; Shi Feng; Lu Xue; Lu Xue; Lu Xue; Jianghua Chen; Jianghua Chen; Jianghua Chen; Hong Jiang; Hong Jiang; Hong Jiang

doi:10.3389/fphys.2021.651690

Frontiers in Physiology (Sep 2021)

Identification of VCAN as Hub Gene for Diabetic Kidney Disease Immune Injury Using Integrated Bioinformatics Analysis

Qiannan Xu,
Qiannan Xu,
Qiannan Xu,
Binjue Li,
Binjue Li,
Binjue Li,
Yucheng Wang,
Yucheng Wang,
Yucheng Wang,
Cuili Wang,
Cuili Wang,
Cuili Wang,
Shi Feng,
Shi Feng,
Shi Feng,
Lu Xue,
Lu Xue,
Lu Xue,
Jianghua Chen,
Jianghua Chen,
Jianghua Chen,
Hong Jiang,
Hong Jiang,
Hong Jiang

Affiliations

Qiannan Xu: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Qiannan Xu: Key Laboratory of Nephropathy, Hangzhou, China
Qiannan Xu: Institute of Nephropathy, Zhejiang University, Hangzhou, China
Binjue Li: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Binjue Li: Key Laboratory of Nephropathy, Hangzhou, China
Binjue Li: Institute of Nephropathy, Zhejiang University, Hangzhou, China
Yucheng Wang: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Yucheng Wang: Key Laboratory of Nephropathy, Hangzhou, China
Yucheng Wang: Institute of Nephropathy, Zhejiang University, Hangzhou, China
Cuili Wang: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Cuili Wang: Key Laboratory of Nephropathy, Hangzhou, China
Cuili Wang: Institute of Nephropathy, Zhejiang University, Hangzhou, China
Shi Feng: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Shi Feng: Key Laboratory of Nephropathy, Hangzhou, China
Shi Feng: Institute of Nephropathy, Zhejiang University, Hangzhou, China
Lu Xue: Department of Otolaryngology Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Lu Xue: Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Lu Xue: Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China
Jianghua Chen: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Jianghua Chen: Key Laboratory of Nephropathy, Hangzhou, China
Jianghua Chen: Institute of Nephropathy, Zhejiang University, Hangzhou, China
Hong Jiang: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Hong Jiang: Key Laboratory of Nephropathy, Hangzhou, China
Hong Jiang: Institute of Nephropathy, Zhejiang University, Hangzhou, China

DOI: https://doi.org/10.3389/fphys.2021.651690
Journal volume & issue: Vol. 12

Abstract

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Background: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease in China. Tubular injury contributes to the progression of DKD. Our study was conducted to explore the differential gene expression profiles between kidneys from patients with DKD and kidney living donors (LDs).Methods: In total, seven DKD and eighteen LD gene expression profiles from the GSE104954 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed in R with the limma package. DEGs were uploaded to the g:Profiler online database to explore the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Ingenuity pathway analysis (IPA) was carried out using online IPA software. Weighted gene co-expression network analysis (WGCNA) was performed using the WGCNA R package. By integrating DEGs and genes from the top 1 phenotype-gene associated module, we determined the hub gene. We next tested the hub gene, VCAN, in the GSE30122 dataset. We also validated the versican levels in human kidney tissues, explored immune cell type enrichment using an online database xCell, and investigated the correlation between cell types and VCAN expression.Results: A total of 563 DEGs was identified. A large number of pathways were involved in the immune response process according to the results of GO, KEGG, and IPA. Using WGCNA, we selected the lightcyan module in which genes showed the strongest correlation with the phenotype and smallest P-value. We also identified VCAN as a hub gene by integrating DEG analysis and WGCNA. Versican expression was upregulated in human diabetic kidney tissue. Moreover, versican was speculated to play a role in immune injury according to the enrichment of functions and signaling pathways. VCAN transcript levels correlate with the assembly of immune cells in the kidney.Conclusion: Immune processes played an essential role in DKD tubulointerstitium injury. The hub gene VCAN contributed to this process.

Published in Frontiers in Physiology

ISSN: 1664-042X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Physiology
Website: https://www.frontiersin.org/journals/physiology

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