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Screening of Diabetic Nephropathy Progression-Related Genes Based on Weighted Gene Co-expression Network Analysis

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Abstract

The purpose of this study is to explore the progression-related genes of diabetic nephropathy (DN) through weighted gene co-expression network analysis (WGCNA). The gene expression dataset GSE14202 was downloaded from the GEO database for differential expression analysis. WGCNA v1.69 was used to perform co-expression analysis on differentially expressed genes. 25 modular genes were selected through WGCNA. The motif enrichment analysis was performed on 25 genes, and 34 motifs were obtained, of which 8 transcription factors (TFs) were differentially expressed. GENIE3 was applied to analyze the expression correlation of 8 differentially expressed TFs and 25 genes. Combined with the predicted TF-target gene relationship, 69 interactions between 8 TFs and 18 genes were obtained. The functional enrichment analysis of 18 genes showed that 7 key genes were obviously enriched in adaptive immune response and were clearly up-regulated in advanced DN patients. The expression of C1S, LAIR1, CD84, SIT1, SASH3, and CD180 in glomerular samples from DN patients was significantly up-regulated in compared with normal samples, and the expression of these genes was negatively correlated with GFR. We observed that in the in vitro cell model of DN, the relative expression levels of 5 key genes (except SASH3) were obviously elevated in the high-glucose group. Five key genes were identified to be related to the progression of DN. The findings of this study may provide new ideas and therapeutic targets for exploring the pathogenesis of DN.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BP:

Biological process

CC:

Cellular component

DEGs:

Differentially expressed genes

DN:

Diabetic nephropathy

GEO:

Gene expression omnibus

GFR:

Glomerular filtration rate

GO:

Gene ontology

GS:

Gene significance

KEGG:

Kyoto encyclopedia of genes and genomes

MF:

Molecular function

MM:

Module membership

TFBS:

Transcription factor binding sites

TFs:

Transcription factors

TOM:

Topological overlap matrix

TTS:

Transcriptional start sites

WGCNA:

Weighted gene co-expression network analysis

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Funding

This work was supported by the Basic Public Welfare Research Program of Zhejiang Province (Grant No. LY20H070001) and Zhejiang Provincial Medical and Health Science and Technology Program (Grant No. 2020KY1042).

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Authors and Affiliations

  1. Department of Nephrology, Taizhou First People’s Hospital, Huangyan Hospital, Wenzhou Medical University, No. 218 Hengjie Road, Dongcheng Street, Huangyan District, Taizhou, 318020, Zhejiang, China

    Ling’an Yu

  2. Department of Endocrinology, Taizhou First People’s Hospital, Huangyan Hospital, Wenzhou Medical University, No. 218 Hengjie Road, Dongcheng Street, Huangyan District, Taizhou, 318020, Zhejiang, China

    Haiying Tao

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  1. Ling’an Yu
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Contributions

LY: brought out the original conceptualization, conducted most of the formal analysis and completed the drafting of the manuscript; HT: collected the research data and reviewed & edited the manuscript. All the authors read and approved the final version of the manuscript.

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Correspondence to Haiying Tao.

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Ethics approval was not required for the present study. All sample information is provided from a public database.

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Yu, L., Tao, H. Screening of Diabetic Nephropathy Progression-Related Genes Based on Weighted Gene Co-expression Network Analysis. Biochem Genet 61, 221–237 (2023). https://doi.org/10.1007/s10528-022-10250-3

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