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http://purl.uniprot.org/citations/29158549http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29158549http://www.w3.org/2000/01/rdf-schema#comment"Proteinuria is closely associated with the progression of chronic kidney diseases (CKD) by producing renal tubulointerstitial fibrosis. Over-activation of hypoxia inducible factor (HIF)-1α has been implicated in the progression of CKD. The present study tested the hypothesis that HIF-1α mediates albumin-induced profibrotic effect in cultured renal proximal tubular cells. Incubation of the cells with albumin (40 μg/ml) for 72 hrs significantly increased the protein levels of HIF-1α, tissue inhibitor of metalloproteinase (TIMP)-1 and collagen-I, which were blocked by HIF-1α shRNA. Albumin also stimulated an epithelial-mesenchymal transition (EMT) as indicated by the decrease in epithelial marker E-cadherin, and the increase in mesenchymal markers α-smooth muscle actin and fibroblast-specific protein 1. HIF-1α shRNA blocked albumin-induced changes in these EMT markers as well. Furthermore, albumin reduced the level of hydroxylated HIF-1α, indicating an inhibition of the activity of prolyl-hydroxylases, enzymes promoting the degradation of HIF-1α. An anti-oxidant ascorbate reversed albumin-induced inhibition of prolyl-hydroxylase activity. Overexpression of prolyl-hydroxylase 2 (PHD2) transgene, a predominant isoform of PHDs in renal tubules, to reduce HIF-1α level significantly attenuated albumin-induced increases in TIMP-1 and collagen-I levels. These results suggest that albumin-induced oxidative stress inhibits PHD activity to accumulate HIF-1α, which mediates albumin-induced profibrotic effects in renal tubular cells."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.org/dc/terms/identifier"doi:10.1038/s41598-017-15972-8"xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/author"Hu J."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/author"Li N."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/author"Zhang F."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/author"Wang W."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/author"Yi F."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/author"Li P.L."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/author"Boini K.M."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/name"Sci Rep"xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/pages"15878"xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/title"Hypoxia inducible factor-1alpha mediates the profibrotic effect of albumin in renal tubular cells."xsd:string
http://purl.uniprot.org/citations/29158549http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/29158549http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29158549
http://purl.uniprot.org/citations/29158549http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29158549
http://purl.uniprot.org/uniprot/#_A6KJ27-mappedCitation-29158549http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29158549
http://purl.uniprot.org/uniprot/#_P59722-mappedCitation-29158549http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29158549
http://purl.uniprot.org/uniprot/A6KJ27http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/29158549
http://purl.uniprot.org/uniprot/P59722http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/29158549