Complement C7 is Specifically Expressed in Mesangial Cells and is a Potential Diagnostic Biomarker for Diabetic Nephropathy and is Regulated by miR-494-3p and miR-574-5p

Hang Guo; Zhiyue Yan; Yonghui Hu; Xitong Huang; Congqing Pan

doi:10.2147/DMSO.S311725

Complement C7 is Specifically Expressed in Mesangial Cells and is a Potential Diagnostic Biomarker for Diabetic Nephropathy and is Regulated by miR-494-3p and miR-574-5p

Diabetes Metab Syndr Obes. 2021 Jul 5:14:3077-3088. doi: 10.2147/DMSO.S311725. eCollection 2021.

Authors

Hang Guo¹, Zhiyue Yan¹, Yonghui Hu¹, Xitong Huang², Congqing Pan¹

Affiliations

¹ NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, People's Republic of China.
² Department of TCM, China Pharmaceutical University, Nanjing, Jiangsu, 211100, People's Republic of China.

Abstract

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, but it remains relatively underdiagnosed.

Objective: In this study, we aimed to explore the key regulatory pathways and potential biomarkers related to DN using integrated bioinformatics analysis and validation.

Methods: First, the microarray data of the GSE30528 and GSE96804 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. Then, weighted gene coexpression network analysis (WGCNA), gene ontology (GO) annotation, gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify key pathways and genes. qRT-PCR and receiver operating characteristic (ROC) curves were used to validate our results. Furthermore, single-cell RNA sequencing (scRNA-seq) data were reanalyzed to investigate the expression specificity of C7 in DN cells. An online database search and luciferase reporter assay identified the target relationship between miRNAs and C7.

Results: The "complement and coagulation cascades" were significantly enriched, and complement C3 and C7 were candidate markers. The receiver operating characteristic (ROC) curve revealed that C7 had significant diagnostic value (AUC=0.865) in DN. Through scRNA-seq reanalysis, we found that C7 was specifically elevated in mesangial (MES) cells of DN. Moreover, we found that the expression of C7 was regulated by miR-494-3p and miR-574-5p.

Conclusion: This is the first study to reveal that C7 is specifically expressed in mesangial cells, is a potential diagnostic biomarker for diabetic nephropathy, and is regulated by miR-494-3p and miR-574-5p.

Keywords: biomarker; complement C7; complement and coagulation cascades; diabetic nephropathy; mesangial (MES) cells; miR-494-3p; miR-574-5p.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81873304) and Tianjin Health Commission Science and Technology Talent Cultivation Project (KJ20022).