Titre
Analysis of the Hypoxic Response in a Mouse Cortical Collecting Duct-Derived Cell Line Suggests That Esrra Is Partially Involved in Hif1α-Mediated Hypoxia-Inducible Gene Expression in mCCD<sub>cl1</sub> Cells.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Keppner, A.
Auteure/Auteur
Maric, D.
Auteure/Auteur
Orlando, IMC
Auteure/Auteur
Falquet, L.
Auteure/Auteur
Hummler, E.
Auteure/Auteur
Hoogewijs, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1422-0067
Statut éditorial
Publié
Date de publication
2022-06-30
Volume
23
Numéro
13
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
The kidney is strongly dependent on a continuous oxygen supply, and is conversely highly sensitive to hypoxia. Controlled oxygen gradients are essential for renal control of solutes and urine-concentrating mechanisms, which also depend on various hormones including aldosterone. The cortical collecting duct (CCD) is part of the aldosterone-sensitive distal nephron and possesses a key function in fine-tuned distal salt handling. It is well known that aldosterone is consistently decreased upon hypoxia. Furthermore, a recent study reported a hypoxia-dependent down-regulation of sodium currents within CCD cells. We thus investigated the possibility that cells from the cortical collecting duct are responsive to hypoxia, using the mouse cortical collecting duct cell line mCCDcl1 as a model. By analyzing the hypoxia-dependent transcriptome of mCCDcl1 cells, we found a large number of differentially-expressed genes (3086 in total logFC< −1 or >1) following 24 h of hypoxic conditions (0.2% O2). A gene ontology analysis of the differentially-regulated pathways revealed a strong decrease in oxygen-linked processes such as ATP metabolic functions, oxidative phosphorylation, and cellular and aerobic respiration, while pathways associated with hypoxic responses were robustly increased. The most pronounced regulated genes were confirmed by RT-qPCR. The low expression levels of Epas1 under both normoxic and hypoxic conditions suggest that Hif-1α, rather than Hif-2α, mediates the hypoxic response in mCCDcl1 cells. Accordingly, we generated shRNA-mediated Hif-1α knockdown cells and found Hif-1α to be responsible for the hypoxic induction of established hypoxically-induced genes. Interestingly, we could show that following shRNA-mediated knockdown of Esrra, Hif-1α protein levels were unaffected, but the gene expression levels of Egln3 and Serpine1 were significantly reduced, indicating that Esrra might contribute to the hypoxia-mediated expression of these and possibly other genes. Collectively, mCCDcl1 cells display a broad response to hypoxia and represent an adequate cellular model to study additional factors regulating the response to hypoxia.
Sujets
PID Serval
serval:BIB_02B6D79CA33B
PMID
Open Access
Oui
Date de création
2023-04-03T07:40:15.897Z
Date de création dans IRIS
2025-05-20T19:04:35Z
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Nom
ijms-23-07262.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
3.01 MB
Format
Adobe PDF
PID Serval
serval:BIB_02B6D79CA33B.P001
URN
urn:nbn:ch:serval-BIB_02B6D79CA33B0
Somme de contrôle
(MD5):720050a7162da40c131cd4f90a6d99eb