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Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics

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 g...

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Autores principales: Zhang, Yu, Shi, Chuanbing, Yang, Yiqiong, Hu, Xiuxiu, Ni, Haifeng, Li, Li, Cheng, Zhengyuan, Huang, Jing, Chen, Pingsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638415/
https://www.ncbi.nlm.nih.gov/pubmed/37949939
http://dx.doi.org/10.1038/s41598-023-46934-y
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author Zhang, Yu
Shi, Chuanbing
Yang, Yiqiong
Hu, Xiuxiu
Ni, Haifeng
Li, Li
Cheng, Zhengyuan
Huang, Jing
Chen, Pingsheng
author_facet Zhang, Yu
Shi, Chuanbing
Yang, Yiqiong
Hu, Xiuxiu
Ni, Haifeng
Li, Li
Cheng, Zhengyuan
Huang, Jing
Chen, Pingsheng
author_sort Zhang, Yu
collection PubMed
description 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.
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spelling pubmed-106384152023-11-11 Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics Zhang, Yu Shi, Chuanbing Yang, Yiqiong Hu, Xiuxiu Ni, Haifeng Li, Li Cheng, Zhengyuan Huang, Jing Chen, Pingsheng Sci Rep Article 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. Nature Publishing Group UK 2023-11-10 /pmc/articles/PMC10638415/ /pubmed/37949939 http://dx.doi.org/10.1038/s41598-023-46934-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Yu
Shi, Chuanbing
Yang, Yiqiong
Hu, Xiuxiu
Ni, Haifeng
Li, Li
Cheng, Zhengyuan
Huang, Jing
Chen, Pingsheng
Identifying key genes related to the peritubular capillary rarefaction in renal interstitial fibrosis by bioinformatics
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638415/
https://www.ncbi.nlm.nih.gov/pubmed/37949939
http://dx.doi.org/10.1038/s41598-023-46934-y
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