Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts

Abstract Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD d...

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Autores principales:	Natallia Shved, Gregor Warsow, Felix Eichinger, David Hoogewijs, Simone Brandt, Peter Wild, Matthias Kretzler, Clemens D. Cohen, Maja T. Lindenmeyer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0b078d380c64c128af4e76a7ea6e241
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spelling	oai:doaj.org-article:d0b078d380c64c128af4e76a7ea6e2412021-12-02T12:32:00ZTranscriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts10.1038/s41598-017-08492-y2045-2322https://doaj.org/article/d0b078d380c64c128af4e76a7ea6e2412017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08492-yhttps://doaj.org/toc/2045-2322Abstract Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD development and progression. In our study, genome-wide expression profiles of more than 200 renal biopsies from patients with different CKD stages revealed significant correlation of HIF-target genes with eGFR in glomeruli and tubulointerstitium. These correlations were positive and negative and in part compartment-specific. Microarrays of proximal tubular cells and podocytes with stable HIF1α and/or HIF2α suppression displayed cell type-specific HIF1/HIF2-dependencies as well as dysregulation of several pathways. WGCNA analysis identified gene sets that were highly coregulated within modules. Characterization of the modules revealed common as well as cell group- and condition-specific pathways, GO-Terms and transcription factors. Gene expression analysis of the hypoxia-interconnected pathways in patients with different CKD stages revealed an increased dysregulation with loss of renal function. In conclusion, our data clearly point to a compartment- and cell type-specific dysregulation of hypoxia-associated gene transcripts and might help to improve the understanding of hypoxia, HIF dysregulation, and transcriptional program response in CKD.Natallia ShvedGregor WarsowFelix EichingerDavid HoogewijsSimone BrandtPeter WildMatthias KretzlerClemens D. CohenMaja T. LindenmeyerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natallia Shved Gregor Warsow Felix Eichinger David Hoogewijs Simone Brandt Peter Wild Matthias Kretzler Clemens D. Cohen Maja T. Lindenmeyer Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
description	Abstract Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD development and progression. In our study, genome-wide expression profiles of more than 200 renal biopsies from patients with different CKD stages revealed significant correlation of HIF-target genes with eGFR in glomeruli and tubulointerstitium. These correlations were positive and negative and in part compartment-specific. Microarrays of proximal tubular cells and podocytes with stable HIF1α and/or HIF2α suppression displayed cell type-specific HIF1/HIF2-dependencies as well as dysregulation of several pathways. WGCNA analysis identified gene sets that were highly coregulated within modules. Characterization of the modules revealed common as well as cell group- and condition-specific pathways, GO-Terms and transcription factors. Gene expression analysis of the hypoxia-interconnected pathways in patients with different CKD stages revealed an increased dysregulation with loss of renal function. In conclusion, our data clearly point to a compartment- and cell type-specific dysregulation of hypoxia-associated gene transcripts and might help to improve the understanding of hypoxia, HIF dysregulation, and transcriptional program response in CKD.
format	article
author	Natallia Shved Gregor Warsow Felix Eichinger David Hoogewijs Simone Brandt Peter Wild Matthias Kretzler Clemens D. Cohen Maja T. Lindenmeyer
author_facet	Natallia Shved Gregor Warsow Felix Eichinger David Hoogewijs Simone Brandt Peter Wild Matthias Kretzler Clemens D. Cohen Maja T. Lindenmeyer
author_sort	Natallia Shved
title	Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
title_short	Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
title_full	Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
title_fullStr	Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
title_full_unstemmed	Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
title_sort	transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d0b078d380c64c128af4e76a7ea6e241
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_version_	1718394244682481664

Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts

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