Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366990413> ?p ?o ?g. }
- W4366990413 endingPage "2288" @default.
- W4366990413 startingPage "2276" @default.
- W4366990413 abstract "ABSTRACT Background The roles of hypoxia and hypoxia inducible factor (HIF) during chronic kidney disease (CKD) are much debated. Interventional studies with HIF-α activation in rodents have yielded contradictory results. The HIF pathway is regulated by prolyl and asparaginyl hydroxylases. While prolyl hydroxylase inhibition is a well-known method to stabilize HIF-α, little is known about the effect asparaginyl hydroxylase factor inhibiting HIF (FIH). Methods We used a model of progressive proteinuric CKD and a model of obstructive nephropathy with unilateral fibrosis. In these models we assessed hypoxia with pimonidazole and vascularization with three-dimensional micro-computed tomography imaging. We analysed a database of 217 CKD biopsies from stage 1 to 5 and we randomly collected 15 CKD biopsies of various severity degrees to assess FIH expression. Finally, we modulated FIH activity in vitro and in vivo using a pharmacologic approach to assess its relevance in CKD. Results In our model of proteinuric CKD, we show that early CKD stages are not characterized by hypoxia or HIF activation. At late CKD stages, some areas of hypoxia are observed, but these are not colocalizing with fibrosis. In mice and in humans, we observed a downregulation of the HIF pathway, together with an increased FIH expression in CKD, according to its severity. Modulating FIH in vitro affects cellular metabolism, as described previously. In vivo, pharmacologic FIH inhibition increases the glomerular filtration rate of control and CKD animals and is associated with decreased development of fibrosis. Conclusions The causative role of hypoxia and HIF activation in CKD progression is questioned. A pharmacological approach of FIH downregulation seems promising in proteinuric kidney disease." @default.
- W4366990413 created "2023-04-27" @default.
- W4366990413 creator A5002135335 @default.
- W4366990413 creator A5009083981 @default.
- W4366990413 creator A5009447131 @default.
- W4366990413 creator A5015359260 @default.
- W4366990413 creator A5016648462 @default.
- W4366990413 creator A5018107103 @default.
- W4366990413 creator A5018589139 @default.
- W4366990413 creator A5029037422 @default.
- W4366990413 creator A5046398504 @default.
- W4366990413 creator A5048320689 @default.
- W4366990413 creator A5048677837 @default.
- W4366990413 creator A5057810440 @default.
- W4366990413 creator A5059102060 @default.
- W4366990413 creator A5063679469 @default.
- W4366990413 creator A5064926938 @default.
- W4366990413 creator A5071397732 @default.
- W4366990413 creator A5073071107 @default.
- W4366990413 creator A5075131805 @default.
- W4366990413 creator A5077352717 @default.
- W4366990413 creator A5085283451 @default.
- W4366990413 creator A5090650208 @default.
- W4366990413 creator A5090798159 @default.
- W4366990413 date "2023-04-24" @default.
- W4366990413 modified "2023-10-17" @default.
- W4366990413 title "Evolution of hypoxia and hypoxia-inducible factor asparaginyl hydroxylase regulation in chronic kidney disease" @default.
- W4366990413 cites W1595792794 @default.
- W4366990413 cites W1975984062 @default.
- W4366990413 cites W1983097616 @default.
- W4366990413 cites W2001480291 @default.
- W4366990413 cites W2026100316 @default.
- W4366990413 cites W2032385561 @default.
- W4366990413 cites W2068238193 @default.
- W4366990413 cites W2073742622 @default.
- W4366990413 cites W2080274549 @default.
- W4366990413 cites W2089692551 @default.
- W4366990413 cites W2096607633 @default.
- W4366990413 cites W2099540110 @default.
- W4366990413 cites W2101068394 @default.
- W4366990413 cites W2101901896 @default.
- W4366990413 cites W2105176807 @default.
- W4366990413 cites W2107751591 @default.
- W4366990413 cites W2122770875 @default.
- W4366990413 cites W2127475414 @default.
- W4366990413 cites W2127622541 @default.
- W4366990413 cites W2127894220 @default.
- W4366990413 cites W2133254081 @default.
- W4366990413 cites W2137571953 @default.
- W4366990413 cites W2141720478 @default.
- W4366990413 cites W2145023430 @default.
- W4366990413 cites W2149424790 @default.
- W4366990413 cites W2150184000 @default.
- W4366990413 cites W2157795344 @default.
- W4366990413 cites W2167279371 @default.
- W4366990413 cites W2170221966 @default.
- W4366990413 cites W2232997241 @default.
- W4366990413 cites W2294795032 @default.
- W4366990413 cites W2740202319 @default.
- W4366990413 cites W2745104857 @default.
- W4366990413 cites W2795707995 @default.
- W4366990413 cites W2948562352 @default.
- W4366990413 cites W2952391626 @default.
- W4366990413 cites W2955193090 @default.
- W4366990413 cites W2963534431 @default.
- W4366990413 cites W2964045421 @default.
- W4366990413 cites W2977682063 @default.
- W4366990413 cites W2996195365 @default.
- W4366990413 cites W2998552676 @default.
- W4366990413 cites W3010708209 @default.
- W4366990413 cites W3019546512 @default.
- W4366990413 cites W3039024065 @default.
- W4366990413 cites W3041847271 @default.
- W4366990413 cites W3094122766 @default.
- W4366990413 cites W3125563499 @default.
- W4366990413 cites W3130258858 @default.
- W4366990413 cites W4210777825 @default.
- W4366990413 cites W4226409442 @default.
- W4366990413 cites W4294107304 @default.
- W4366990413 doi "https://doi.org/10.1093/ndt/gfad075" @default.
- W4366990413 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37096392" @default.
- W4366990413 hasPublicationYear "2023" @default.
- W4366990413 type Work @default.
- W4366990413 citedByCount "0" @default.
- W4366990413 crossrefType "journal-article" @default.
- W4366990413 hasAuthorship W4366990413A5002135335 @default.
- W4366990413 hasAuthorship W4366990413A5009083981 @default.
- W4366990413 hasAuthorship W4366990413A5009447131 @default.
- W4366990413 hasAuthorship W4366990413A5015359260 @default.
- W4366990413 hasAuthorship W4366990413A5016648462 @default.
- W4366990413 hasAuthorship W4366990413A5018107103 @default.
- W4366990413 hasAuthorship W4366990413A5018589139 @default.
- W4366990413 hasAuthorship W4366990413A5029037422 @default.
- W4366990413 hasAuthorship W4366990413A5046398504 @default.
- W4366990413 hasAuthorship W4366990413A5048320689 @default.
- W4366990413 hasAuthorship W4366990413A5048677837 @default.
- W4366990413 hasAuthorship W4366990413A5057810440 @default.
- W4366990413 hasAuthorship W4366990413A5059102060 @default.