| Autor: |
Natallia Shved, Gregor Warsow, Felix Eichinger, David Hoogewijs, Simone Brandt, Peter Wild, Matthias Kretzler, Clemens D. Cohen, Maja T. Lindenmeyer |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 7, Iss 1, Pp 1-17 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-017-08492-y |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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