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Identification of transcription factors related to diabetic tubulointerstitial injury

BACKGROUND: Diabetic nephropathy (DN) is a main cause of chronic renal failure. Despite decades of extensive study, the molecular mechanisms underlying diabetic tubulointerstitial injury remain unclear. We aim to identify key transcription factor genes involved in diabetic tubulointerstitial injury....

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Autores principales: Liu, Jialu, Duan, Guangzhong, Yang, Wenxia, Zhang, Shumin, Liu, Fuyou, Peng, Youming, Sun, Lin, Liu, Yu, Xiao, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053902/
https://www.ncbi.nlm.nih.gov/pubmed/36978091
http://dx.doi.org/10.1186/s12967-023-04069-8
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author Liu, Jialu
Duan, Guangzhong
Yang, Wenxia
Zhang, Shumin
Liu, Fuyou
Peng, Youming
Sun, Lin
Liu, Yu
Xiao, Li
author_facet Liu, Jialu
Duan, Guangzhong
Yang, Wenxia
Zhang, Shumin
Liu, Fuyou
Peng, Youming
Sun, Lin
Liu, Yu
Xiao, Li
author_sort Liu, Jialu
collection PubMed
description BACKGROUND: Diabetic nephropathy (DN) is a main cause of chronic renal failure. Despite decades of extensive study, the molecular mechanisms underlying diabetic tubulointerstitial injury remain unclear. We aim to identify key transcription factor genes involved in diabetic tubulointerstitial injury. METHODS: A microarray dataset (GSE30122) from Gene Expression Omnibus (GEO) was downloaded. A total of 38 transcription factor genes based on 166 differentially expressed genes (DEGs) were identified by UCSC_TFBS. RESULTS: The regulatory network showed connections between the top 10 transcription factors and their target DEGs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of targeted DEGs indicated that extracellular space, extracellular exosome, cell surface and complement and coagulation cascades were most significantly enriched. Utilizing Nephroseq v5 online platform, the mRNA expression pattern analysis of transcription factor genes demonstrated that mRNA expression of CDC5, CEBPA, FAC1, HFH1, IRF1, NFE2 and TGIF1 increased in renal tubulointerstitium of DN patients compared with normal controls while that of CEBPB and FOXO4 decreased in renal tubulointerstitium of DN patients compared with normal controls. Correlation analysis between mRNA expression of transcription factor genes in renal tubulointerstitium and clinical features showed that AP1, BACH1, CDC5, FAC1, FOXD1, FOXJ2, FOXO1, FOXO4, HFH1, IRF1, POU3F2, SOX5, SOX9, RSRFC4, S8 and TGIF1 may be related to diabetic tubulointerstitial injury. CONCLUSIONS: (1) CDC5, FAC1, FOXO4, HFH1, IRF1 and TGIF1 may be key transcription factor genes. (2)Transcription factors involved in diabetic tubulointerstitial injury may become prospective targets for diagnosis and treatment of DN. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04069-8.
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spelling pubmed-100539022023-03-30 Identification of transcription factors related to diabetic tubulointerstitial injury Liu, Jialu Duan, Guangzhong Yang, Wenxia Zhang, Shumin Liu, Fuyou Peng, Youming Sun, Lin Liu, Yu Xiao, Li J Transl Med Research BACKGROUND: Diabetic nephropathy (DN) is a main cause of chronic renal failure. Despite decades of extensive study, the molecular mechanisms underlying diabetic tubulointerstitial injury remain unclear. We aim to identify key transcription factor genes involved in diabetic tubulointerstitial injury. METHODS: A microarray dataset (GSE30122) from Gene Expression Omnibus (GEO) was downloaded. A total of 38 transcription factor genes based on 166 differentially expressed genes (DEGs) were identified by UCSC_TFBS. RESULTS: The regulatory network showed connections between the top 10 transcription factors and their target DEGs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of targeted DEGs indicated that extracellular space, extracellular exosome, cell surface and complement and coagulation cascades were most significantly enriched. Utilizing Nephroseq v5 online platform, the mRNA expression pattern analysis of transcription factor genes demonstrated that mRNA expression of CDC5, CEBPA, FAC1, HFH1, IRF1, NFE2 and TGIF1 increased in renal tubulointerstitium of DN patients compared with normal controls while that of CEBPB and FOXO4 decreased in renal tubulointerstitium of DN patients compared with normal controls. Correlation analysis between mRNA expression of transcription factor genes in renal tubulointerstitium and clinical features showed that AP1, BACH1, CDC5, FAC1, FOXD1, FOXJ2, FOXO1, FOXO4, HFH1, IRF1, POU3F2, SOX5, SOX9, RSRFC4, S8 and TGIF1 may be related to diabetic tubulointerstitial injury. CONCLUSIONS: (1) CDC5, FAC1, FOXO4, HFH1, IRF1 and TGIF1 may be key transcription factor genes. (2)Transcription factors involved in diabetic tubulointerstitial injury may become prospective targets for diagnosis and treatment of DN. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04069-8. BioMed Central 2023-03-29 /pmc/articles/PMC10053902/ /pubmed/36978091 http://dx.doi.org/10.1186/s12967-023-04069-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Jialu
Duan, Guangzhong
Yang, Wenxia
Zhang, Shumin
Liu, Fuyou
Peng, Youming
Sun, Lin
Liu, Yu
Xiao, Li
Identification of transcription factors related to diabetic tubulointerstitial injury
title Identification of transcription factors related to diabetic tubulointerstitial injury
title_full Identification of transcription factors related to diabetic tubulointerstitial injury
title_fullStr Identification of transcription factors related to diabetic tubulointerstitial injury
title_full_unstemmed Identification of transcription factors related to diabetic tubulointerstitial injury
title_short Identification of transcription factors related to diabetic tubulointerstitial injury
title_sort identification of transcription factors related to diabetic tubulointerstitial injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053902/
https://www.ncbi.nlm.nih.gov/pubmed/36978091
http://dx.doi.org/10.1186/s12967-023-04069-8
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