Journal
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
Volume 14, Issue -, Pages 3077-3088Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DMSO.S311725
Keywords
diabetic nephropathy; mesangial (MES) cells; complement and coagulation cascades; complement C7; miR-494-3p; miR-574-5p; biomarker
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Funding
- National Natural Science Foundation of China [81873304]
- Tianjin Health Commission Science and Technology Talent Cultivation Project [KJ20022]
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The study revealed that C7 is specifically expressed in mesangial cells of diabetic nephropathy and may serve as a potential diagnostic biomarker. The expression of C7 is regulated by miR494-3p and miR-574-5p. This has important implications for understanding the pathogenesis of DN and potential therapeutic targets.
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 miR494-3p and miR-574-5p.
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