
Identification of key genes and pathways in diabetic nephropathy by bioinformatics analysis
Author(s) -
Geng Xiaodong,
Wang Weiwei,
Feng Zhe,
Liu Ran,
Cheng Xiaolong,
Shen Wanjun,
Dong Zheyi,
Cai Guangyan,
Chen Xiangmei,
Hong Quan,
Wu Di
Publication year - 2019
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12986
Subject(s) - chromatin immunoprecipitation , transcription factor , diabetic nephropathy , biology , microbiology and biotechnology , gene expression , medicine , gene , promoter , kidney , genetics
Aims/Introduction The aim of the present study was to identify candidate differentially expressed genes ( DEG s) and pathways using bioinformatics analysis, and to improve our understanding of the cause and potential molecular events of diabetic nephropathy. Materials and Methods Two cohort profile datasets ( GSE 30528 and GSE 33744) were integrated and used for deep analysis. We sorted DEG s and analyzed differential pathway enrichment. DEG ‐associated ingenuity pathway analysis was carried out. The screened gene expression feature was verified in the db / db mouse kidney cortex. Then, rat mesangial cells cultured with high‐concentration glucose were used for verification. The target genes of transcriptional factor E26 transformation‐specific‐1 (ETS1) were predicted with online tools and validated using chromatin immunoprecipitation assay quantitative polymerase chain reaction . Results The two GSE datasets identified 89 shared DEG s; 51 were upregulated; and 38 were downregulated. Most of the DEG s were significantly enriched in cell adhesion, the plasma membrane, the extracellular matrix and the extracellular region. Quantitative reverse transcription polymerase chain reaction analysis validated the upregulated expression of Itgb2 , Cd44 , Sell , Fn1 , Tgfbi and Il7r , and the downregulated expression of Igfbp2 and Cd55 in the db / db mouse kidney cortex. Chromatin immunoprecipitation assay quantitative polymerase chain reaction showed that Itgb2 was the target gene of transcription factor Ets1. ETS 1 knockdown in rat mesangial cells decreased integrin subunit beta 2 expression. Conclusion We found that EST 1 functioned as an important transcription factor in diabetic nephropathy development through the promotion of integrin subunit beta 2 expression. EST 1 might be a drug target for diabetic nephropathy treatment.