Shved, Natallia Warsow, Gregor Eichinger, Felix Hoogewijs, David Brandt, Simone Wild, Peter Kretzler, Matthias Cohen, Clemens D. Lindenmeyer, Maja T. 2017-08-17 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. application/pdf https://folia.unifr.ch/global/documents/306023 https://folia.unifr.ch/documents/306023/files/hoo_tbn.pdf https://folia.unifr.ch/documents/306023/files/hoo_tbn_sm1.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-08492-y info:eu-repo/semantics/openAccess License undefined Scientific Reports. - 2017, vol. 7, no. 1, p. 8576 info:eu-repo/classification/udc/57 Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts http://purl.org/coar/resource_type/c_6501