Exploring the Differences in Molecular Mechanisms and Key Biomarkers Between Membranous Nephropathy and Lupus Nephritis Using Integrated Bioinformatics Analysis.

Zhaocheng Dong,Qihan Zhao,Wenbin Liu,Hongliang Rui,Zhendong Feng,Hanxue Jiang,Baoli Liu,Haoran Dai,Wei Jing Liu,Fei Liu

doi:10.3389/fgene.2021.770902

Abstract

Background: Both membranous nephropathy (MN) and lupus nephritis (LN) are autoimmune kidney disease. In recent years, with the deepening of research, some similarities have been found in the pathogenesis of these two diseases. However, the mechanism of their interrelationship is not clear. The purpose of this study was to investigate the differences in molecular mechanisms and key biomarkers between MN and LN. Method: The expression profiles of GSE99325, GSE99339, GSE104948 and GSE104954 were downloaded from GEO database, and the differentially expressed genes (DEGs) of MN and LN samples were obtained. We used Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for enrichment analysis of DEGs. A protein-protein interaction (PPI) network of DEGs was constructed using Metascape. We filtered DEGs with NetworkAnalyst. Finally, we used receiver operating characteristic (ROC) analysis to identify the most significant DEGs for MN and LN. Result: Compared with LN in the glomerulus, 14 DEGs were up-regulated and 77 DEGs were down-regulated in MN. Compared with LN in renal tubules, 21 DEGs were down-regulated, but no up-regulated genes were found in MN. According to the result of GO and KEGG enrichment, PPI network and Networkanalyst, we screened out six genes (IFI6, MX1, XAF1, HERC6, IFI44L, IFI44). Interestingly, among PLA2R, THSD7A and NELL1, which are the target antigens of podocyte in MN, the expression level of NELL1 in MN glomerulus is significantly higher than that of LN, while there is no significant difference in the expression level of PLA2R and THSD7A. Conclusion: Our study provides new insights into the pathogenesis of MN and LN by analyzing the differences in gene expression levels between MN and LN kidney samples, and is expected to be used to prepare an animal model of MN that is more similar to human.

Highlights

membranous nephropathy (MN) is one of the pathological types of primary glomerular diseases (Couser, 2017)
Our study provides new insights into the pathogenesis of MN and lupus nephritis (LN) by analyzing the differences in gene expression levels between MN and LN kidney samples, Difference Between MN and LN
The results showed that IFI44 and MX dynamin like GTPase 1 (MX1) had the best diagnostic value in differentiating MN patients from LN patients in glomerular group, with area under curve (AUC) of 0.980 and 0.967, respectively

Summary

Introduction

MN is one of the pathological types of primary glomerular diseases (Couser, 2017). It is characterized by diffuse glomerular lesions, thickening of capillary walls, and deposition of autoantibodies in situ immune complexes directly with glomerular antigens under the epithelium. Due to the stimulation of polluted air, neutrophils and macrophages in alveoli form extracellular traps, enabling PLA2R to be recognized as its own antigen. These extracellular traps, which do not contain cytoskeletal proteins, are made of nucleic acid material (Goggs et al, 2020). In systemic lupus erythematosus (SLE), autoantibodies directly target nuclear antigens, including DNA (dsDNA and ssDNA), histones and ribonucleoproteins (Thong and Olsen, 2017). Both membranous nephropathy (MN) and lupus nephritis (LN) are autoimmune kidney disease.

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Conclusion