Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification
Diabetic nephropathy (DN) is the most important cause of end-stage renal disease with a poorer prognosis and high economic burdens of medical treatments. It is of great research value and clinical significance to explore potential gene targets of renal tubulointerstitial lesions in DN. To properly i...
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| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/7907708 |
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| author | Jiayi Yang Li Peng Yuqiu Tian Wenbin Tang Linlin Peng Jianping Ning Dongjie Li Yun Peng |
| author_facet | Jiayi Yang Li Peng Yuqiu Tian Wenbin Tang Linlin Peng Jianping Ning Dongjie Li Yun Peng |
| author_sort | Jiayi Yang |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is the most important cause of end-stage renal disease with a poorer prognosis and high economic burdens of medical treatments. It is of great research value and clinical significance to explore potential gene targets of renal tubulointerstitial lesions in DN. To properly identify key genes associated with tubulointerstitial injury of DN, we initially performed a weighted gene coexpression network analysis of the dataset to screen out two nonconserved gene modules (dark orange and dark red). The regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, PI3K-Akt signaling pathway, p38MAPK cascade, and Th1 and Th2 cell differentiation were primarily included in Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these two modules. Next, 199 differentially expressed genes (DEGs) were identified via the limma package. Then, the GO annotation and KEGG pathways of the DEGs were primarily enriched in extracellular matrix (ECM) organization, epithelial cell migration, cell adhesion molecules (CAMs), NF-kappa B signaling pathway, and ECM-receptor interaction. Gene set enrichment analysis showed that in the DN group, the interaction of ECM-receptor, CAMs, the interaction of cytokine-cytokine receptor, and complement and coagulation cascade pathways were significantly activated. Eleven key genes, including ALB, ANXA1, ANXA2, C3, CCL2, CLU, EGF, FOS, PLG, TIMP1, and VCAM1, were selected by constructing a protein-protein interaction network, and expression validation, ECM-related pathways, and glomerular filtration rate correlation analysis were performed in the validated dataset. The upregulated expression of hub genes ANXA2 and FOS was verified by real-time quantitative PCR in HK-2 cells treated with high glucose. This study revealed potential regulatory mechanisms of renal tubulointerstitial damage and highlighted the crucial role of extracellular matrix in DN, which may promote the identification of new biomarkers and therapeutic targets. |
| format | Article |
| id | doaj-art-ded3e9dea81a4c1cbec52fd3ac617aca |
| institution | OA Journals |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-ded3e9dea81a4c1cbec52fd3ac617aca2025-08-20T02:21:20ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/7907708Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment VerificationJiayi Yang0Li Peng1Yuqiu Tian2Wenbin Tang3Linlin Peng4Jianping Ning5Dongjie Li6Yun Peng7Department of GeriatricsDepartment of OphthalmologyDepartment of Infectious DiseaseDepartment of NephrologyDepartment of GeriatricsDepartment of NephrologyDepartment of GeriatricsDepartment of GeriatricsDiabetic nephropathy (DN) is the most important cause of end-stage renal disease with a poorer prognosis and high economic burdens of medical treatments. It is of great research value and clinical significance to explore potential gene targets of renal tubulointerstitial lesions in DN. To properly identify key genes associated with tubulointerstitial injury of DN, we initially performed a weighted gene coexpression network analysis of the dataset to screen out two nonconserved gene modules (dark orange and dark red). The regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, PI3K-Akt signaling pathway, p38MAPK cascade, and Th1 and Th2 cell differentiation were primarily included in Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these two modules. Next, 199 differentially expressed genes (DEGs) were identified via the limma package. Then, the GO annotation and KEGG pathways of the DEGs were primarily enriched in extracellular matrix (ECM) organization, epithelial cell migration, cell adhesion molecules (CAMs), NF-kappa B signaling pathway, and ECM-receptor interaction. Gene set enrichment analysis showed that in the DN group, the interaction of ECM-receptor, CAMs, the interaction of cytokine-cytokine receptor, and complement and coagulation cascade pathways were significantly activated. Eleven key genes, including ALB, ANXA1, ANXA2, C3, CCL2, CLU, EGF, FOS, PLG, TIMP1, and VCAM1, were selected by constructing a protein-protein interaction network, and expression validation, ECM-related pathways, and glomerular filtration rate correlation analysis were performed in the validated dataset. The upregulated expression of hub genes ANXA2 and FOS was verified by real-time quantitative PCR in HK-2 cells treated with high glucose. This study revealed potential regulatory mechanisms of renal tubulointerstitial damage and highlighted the crucial role of extracellular matrix in DN, which may promote the identification of new biomarkers and therapeutic targets.http://dx.doi.org/10.1155/2022/7907708 |
| spellingShingle | Jiayi Yang Li Peng Yuqiu Tian Wenbin Tang Linlin Peng Jianping Ning Dongjie Li Yun Peng Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification Journal of Immunology Research |
| title | Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification |
| title_full | Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification |
| title_fullStr | Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification |
| title_full_unstemmed | Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification |
| title_short | Identification of Hub Genes Involved in Tubulointerstitial Injury in Diabetic Nephropathy by Bioinformatics Analysis and Experiment Verification |
| title_sort | identification of hub genes involved in tubulointerstitial injury in diabetic nephropathy by bioinformatics analysis and experiment verification |
| url | http://dx.doi.org/10.1155/2022/7907708 |
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