Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co-Expression Network Analysis

Yuanyuan Han; Liangzi Jin; Liangzhi Wang; LAN WEI; CHAO TU

doi:10.1159/000531288

Kidney & Blood Pressure Research (Jun 2023)

Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co-Expression Network Analysis

Yuanyuan Han,
Liangzi Jin,
Liangzhi Wang,
LAN WEI,
CHAO TU

Affiliations

Yuanyuan Han: Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
Liangzi Jin: Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
Liangzhi Wang: Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
LAN WEI: Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China
CHAO TU: Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China

DOI: https://doi.org/10.1159/000531288

Abstract

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Introduction: Diabetic nephropathy (DN) is related to type 1 and type 2 diabetes. They are the leading cause of end-stage renal disease, but the underling specific pathogenesis of DN is not yet clear. Our study was conducted to explore how DN changed the transcriptome profiles in the kidney. Methods: The gene expression profile of microdissected glomeruli of 41 type 2 DN patients and 20 healthy controls were included. The sample dataset GSE96804 was obtained from the GEO database. Differentially expressed genes (DEGs) were analyzed in R with the limma package and the important modules were found by weighted gene co-expression network analysis (WGCNA) clustering. The modules were then analyzed based on Gene Ontology (GO) gene set enrichment analysis, and the hub genes were found out. We next validated the hub gene, PDK4, in a cell model of DN. We also constructed the PDK4-related PPI network to investigate the correlation between PDK4 expression and other genes. Results: Heatmap and volcano map were drawn to illustrate the mRNA expression profile of 1,204 DEGs in both samples of DN patients and the control group. Using WGCNA, we selected the blue module in which genes showed the strongest correlation with the phenotype and the smallest p value. We also identified PDK4 as a hub gene. PDK4 expression was upregulated in human diabetic kidney tissue. Moreover, PDK4 was speculated to play a role in glomerular basement membrane development and kidney development according to the enrichment of functions and signaling pathways. Furthermore, PDK4 and two key genes GSTA2 and G6PC protein expression were verified highly expressed in the cell model of DN. Conclusion: During the pathogenesis of DN, many genes may change expression in a coordinated manner. The discovery of PDK4 as key gene using WGCNA is of great significance for the development of new treatment strategies to block the development of DN.

Published in Kidney & Blood Pressure Research

ISSN: 1420-4096 (Print); 1423-0143 (Online)
Publisher: Karger Publishers
Country of publisher: Switzerland
LCC subjects: Medicine: Dermatology; Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Internal medicine: Specialties of internal medicine: Diseases of the genitourinary system. Urology
Website: http://www.karger.com/kbr

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