Abstract: TH-PO890
A Comprehensive Bioinformatics Analysis Reveals the Pivotal Role of Tubulopathy in Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Zhou, Leting, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Liu, Xiaobin, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Zhang, Zhijian, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Zhang, Xiran, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Xue, Jing, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Liu, Bin, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Wang, Liang, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
- Sun, Zhuxing, Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu, China
Background
Diabetic nephropathy(DN) is one of the main causes of ESKD worldwide. However, there is still a lack of a comprehensive understanding of the unique molecular mechanism of DN.
Methods
Over 250 Affymetrix microarray datasets of human glomerular and tubulointerstitial tissues were collected (Table 1) . Next, a linear model was constructed, and the empirical Bayes method was used to select the unique differentially expressed genes (DEGs) of DN. The DEGs were further analyzed using the enrichment analysis. Finally, the protein-protein interaction networks(PINs) with established physical interaction were constructed, and based on the networks, hub genes were selected.
Results
A total of 980 unique DEGs were identified. Enrichment analysis revealed that a wide arrange of pathways are dysregulated in the pathogenesis of DN. Notably, the upregulated DEGs of tubulointerstitial compartment are mainly enriched in pathways related to glycosylation and immune responses, while the downregulated DEGs are strongly related to metabolism disorders(Figure 1) . Moreover, a complex interaction network were found among the DEGs of tubulointerstitial compartment. Lastly, a list of genes, including EGFR, SUZ12 and TERF1, were identified as hub genes.
Conclusion
This bioinformatic analysis suggests that tubulopathy might play a pivotal role in the pathogenesis of DN.
Table 1
| Number of cases | Number of controls | Resources | Platforms | |
| DN Glomeruli | 7 | 18 | GSE37463, GSE47185 | Affymetrix U133 Plus 2.0 |
| DN Tubules | 11 | 22 | GSE35489, GSE47185 | Affymetrix U133 A |
| HN Glomeruli | 15 | 22 | GSE47185, GSE37463 | Affymetrix U133 A |
| HN Tubules | 21 | 22 | GSE47185, GSE37463 | Affymetrix U133 A |
| IgAN Glomeruli | 43 | 22 | GSE37463,GSE21785, GSE20602 | Affymetrix U133 A |
| IgAN Tubules | 25 | 22 | GSE35489, GSE47185 | Affymetrix U133 A |
| MN Glomeruli | 18 | 22 | GSE47185, GSE37463,GSE21785, GSE20602 | Affymetrix U133 A |
| MN Tubules | 18 | 22 | GSE35489, GSE47185 | Affymetrix U133 A |
| FSGS Glomeruli | 23 | 40 | GSE37463, GSE47185, GSE20602, GSE21785 | Affymetrix U133 A Affymetrix U133 Plus 2.0 |
| FSGS Tubules | 12 | 22 | GSE35489, GSE47185 | Affymetrix U133 A |
Funding
- Government Support - Non-U.S.