Zhaocheng Dong1,2, Yunling Geng1,2, Pingna Zhang1,2, Jingyi Tang1,2, Zijing Cao1,2, Huijuan Zheng1,2, Jing Guo1,2, Chao Zhang1,2, Baoli Liu3, Wei Jing Liu1,2. 1. Dongzhimen Hospital, Beijing University of Chinese Medicine Beijing, China. 2. Renal Research Institution of Beijing University of Chinese Medicine, Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine Beijing, China. 3. Beijing Hospital of Traditional Chinese Medicine, Capital Medical University Beijing, China.
Abstract
OBJECTIVES: Membranous nephropathy (MN) is an autoimmune nephropathy. The incidence of MN is increasing gradually in recent years. Previous studies focused on antibody production, complement activation and podocyte injury in MN. However, the etiology and underlying mechanism of MN remain to be further studied. METHODS: GSE104948 and GSE108109 of glomerular expression profile were downloaded from Gene Expression Omnibus (GEO) database, GSE47184, GSE99325, GSE104954, GSE108112, GSE133288 of renal tubule expression profile, and GSE73953 of peripheral blood mononuclear cells (PBMCs) expression profile. After data integration by Networkanalyst, differentially expressed genes (DEGs) between MN and healthy samples were obtained. DEGs were enriched in gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks of these genes were constructed through Metascape, etc. We further understood the function of hub genes through gene set enrichment analysis (GSEA). The diagnostic value of DEGs in MN was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: A total of 3 genes (TP53, HDAC5, and SLC2A3) were screened out. Among them, the up-regulated TP53 expression may be closely related to MN renal pathological changes. However, the expression of MN podocyte target antigen was not significantly different from that of healthy controls. In addition, the changes of Wnt signaling pathway in PBMCs and the effects of SLC2A3 on the differentiation of M2 monocyte need further study. CONCLUSION: It is difficult to unify a specific mechanism for the changes of glomerulus, renal tubules and PBMCs in MN patients. This may be related to the pathogenesis, pathology and immune characteristics of MN. MN podocyte target antigen may not be the root cause of the disease, but a stage result in the pathogenesis process. AJTR
OBJECTIVES: Membranous nephropathy (MN) is an autoimmune nephropathy. The incidence of MN is increasing gradually in recent years. Previous studies focused on antibody production, complement activation and podocyte injury in MN. However, the etiology and underlying mechanism of MN remain to be further studied. METHODS: GSE104948 and GSE108109 of glomerular expression profile were downloaded from Gene Expression Omnibus (GEO) database, GSE47184, GSE99325, GSE104954, GSE108112, GSE133288 of renal tubule expression profile, and GSE73953 of peripheral blood mononuclear cells (PBMCs) expression profile. After data integration by Networkanalyst, differentially expressed genes (DEGs) between MN and healthy samples were obtained. DEGs were enriched in gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks of these genes were constructed through Metascape, etc. We further understood the function of hub genes through gene set enrichment analysis (GSEA). The diagnostic value of DEGs in MN was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: A total of 3 genes (TP53, HDAC5, and SLC2A3) were screened out. Among them, the up-regulated TP53 expression may be closely related to MN renal pathological changes. However, the expression of MN podocyte target antigen was not significantly different from that of healthy controls. In addition, the changes of Wnt signaling pathway in PBMCs and the effects of SLC2A3 on the differentiation of M2 monocyte need further study. CONCLUSION: It is difficult to unify a specific mechanism for the changes of glomerulus, renal tubules and PBMCs in MN patients. This may be related to the pathogenesis, pathology and immune characteristics of MN. MN podocyte target antigen may not be the root cause of the disease, but a stage result in the pathogenesis process. AJTR
Authors: Trevor P Fidler; Elizabeth A Middleton; Jesse W Rowley; Luc H Boudreau; Robert A Campbell; Rhonda Souvenir; Trevor Funari; Nicolas Tessandier; Eric Boilard; Andrew S Weyrich; E Dale Abel Journal: Arterioscler Thromb Vasc Biol Date: 2017-06-29 Impact factor: 8.311