Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics
Abstract Renal interstitial fibrosis (RIF) is a key feature of progressive chronic kidney disease (CKD), characterized by tubular epithelial cell (TEC) hypoxia and peritubular capillary (PTC) rarefaction. However, the mechanisms underlying these processes remain poorly understood. To address this kn...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46934-y |
| _version_ | 1797630233253249024 |
|---|---|
| author | Yu Zhang Chuanbing Shi Yiqiong Yang Xiuxiu Hu Haifeng Ni Li Li Zhengyuan Cheng Jing Huang Pingsheng Chen |
| author_facet | Yu Zhang Chuanbing Shi Yiqiong Yang Xiuxiu Hu Haifeng Ni Li Li Zhengyuan Cheng Jing Huang Pingsheng Chen |
| author_sort | Yu Zhang |
| collection | DOAJ |
| description | Abstract Renal interstitial fibrosis (RIF) is a key feature of progressive chronic kidney disease (CKD), characterized by tubular epithelial cell (TEC) hypoxia and peritubular capillary (PTC) rarefaction. However, the mechanisms underlying these processes remain poorly understood. To address this knowledge gap, we conducted a comparative transcriptome analysis of hypoxic and normoxic HK-2 cells, identifying 572 differentially expressed genes (DEGs). Subsequent Gene Ontology (GO), protein‒protein interaction (PPI) network, and hub gene analyses revealed significant enrichment of DEGs in the HIF-1 signaling pathway based on KEGG enrichment analysis. To further explore TEC modulation under hypoxic conditions, we performed chromatin immunoprecipitation (ChIP) sequencing targeting HIF-1α, identifying 2915 genes potentially regulated by HIF-1α. By comparing RNA sequencing and ChIP sequencing data, we identified 43 overlapping DEGs. By performing GO analysis and peak annotation with IGV, we identified two candidate molecules, VEGFA and BTG1, that are associated with angiogenesis and whose gene sequences were reliably bound by HIF-1α. Our study elucidates the molecular mechanisms underlying RIF, providing valuable insights for potential therapeutic interventions. |
| first_indexed | 2024-03-11T11:05:17Z |
| format | Article |
| id | doaj.art-54a1be1096ff45308fdc26eb99e04ae5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:05:17Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-54a1be1096ff45308fdc26eb99e04ae52023-11-12T12:16:25ZengNature PortfolioScientific Reports2045-23222023-11-0113111510.1038/s41598-023-46934-yIdentifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformaticsYu Zhang0Chuanbing Shi1Yiqiong Yang2Xiuxiu Hu3Haifeng Ni4Li Li5Zhengyuan Cheng6Jing Huang7Pingsheng Chen8Department of Pathology, School of Medicine, Southeast UniversityDepartment of Pathology, Pukou Branch of Jiangsu People’s HospitalDepartment of Pathology, School of Medicine, Southeast UniversityDepartment of Pathology, School of Medicine, Southeast UniversityInstitute of Nephrology, Zhong Da Hospital, School of Medicine, Southeast UniversityDepartment of Pathology, School of Medicine, Southeast UniversityDepartment of Internal Medicine, Ma’anshan People’s Hospital Affiliated to Medical School of Southeast UniversityDepartment of Respiratory and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Pathology, School of Medicine, Southeast UniversityAbstract Renal interstitial fibrosis (RIF) is a key feature of progressive chronic kidney disease (CKD), characterized by tubular epithelial cell (TEC) hypoxia and peritubular capillary (PTC) rarefaction. However, the mechanisms underlying these processes remain poorly understood. To address this knowledge gap, we conducted a comparative transcriptome analysis of hypoxic and normoxic HK-2 cells, identifying 572 differentially expressed genes (DEGs). Subsequent Gene Ontology (GO), protein‒protein interaction (PPI) network, and hub gene analyses revealed significant enrichment of DEGs in the HIF-1 signaling pathway based on KEGG enrichment analysis. To further explore TEC modulation under hypoxic conditions, we performed chromatin immunoprecipitation (ChIP) sequencing targeting HIF-1α, identifying 2915 genes potentially regulated by HIF-1α. By comparing RNA sequencing and ChIP sequencing data, we identified 43 overlapping DEGs. By performing GO analysis and peak annotation with IGV, we identified two candidate molecules, VEGFA and BTG1, that are associated with angiogenesis and whose gene sequences were reliably bound by HIF-1α. Our study elucidates the molecular mechanisms underlying RIF, providing valuable insights for potential therapeutic interventions.https://doi.org/10.1038/s41598-023-46934-y |
| spellingShingle | Yu Zhang Chuanbing Shi Yiqiong Yang Xiuxiu Hu Haifeng Ni Li Li Zhengyuan Cheng Jing Huang Pingsheng Chen Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics Scientific Reports |
| title | Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics |
| title_full | Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics |
| title_fullStr | Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics |
| title_full_unstemmed | Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics |
| title_short | Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics |
| title_sort | identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics |
| url | https://doi.org/10.1038/s41598-023-46934-y |
| work_keys_str_mv | AT yuzhang identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT chuanbingshi identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT yiqiongyang identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT xiuxiuhu identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT haifengni identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT lili identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT zhengyuancheng identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT jinghuang identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics AT pingshengchen identifyingkeygenesrelatedtotheperitubularcapillaryrarefactioninrenalinterstitialfibrosisbybioinformatics |