Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death
Authors
García Pastor, Coral; Benito Martínez, Selma; Bosch Martínez, Ricardo José; Fernández Martínez, Ana Belén; Lucio Cazaña, Francisco Javier deIdentifiers
Permanent link (URI): http://hdl.handle.net/10017/59078DOI: 10.1038/s41598-021-86219-w
ISSN: 2045-2322
Date
2021Affiliation
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas; Universidad de Alcalá. Departamento de Biología de SistemasFunders
Ministerio de Ciencia e Innovación
Universidad de Alcalá
Comunidad de Madrid
Bibliographic citation
Scientific Reports, 2021, v. 11, n. 7047, p. 1-11
Project
info:eu-repo/grantAgreement/MICINN//SAF2014-53218-R/ES/
info:eu-repo/grantAgreement/UAH//UAH-GP2019-4/ES/
info:eu-repo/grantAgreement/CAM//B2017-BMD-3686/ES/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© The Authors
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Proximal tubular cells (PTC) are particularly vulnerable to hypoxia-induced apoptosis, a relevant factor for kidney disease. We hypothesized here that PTC death under hypoxia is mediated by cyclooxygenase (COX-2)-dependent production of prostaglandin E2 (PGE2), which was confirmed in human proximal tubular HK-2 cells because hypoxia (1% O2)- induced apoptosis (i) was prevented by a COX-2 inhibitor and by antagonists of prostaglandin (EP) receptors and (ii) was associated to an increase in intracellular PGE2 (iPGE2) due to hypoxia-inducible factor-1?-dependent transcriptional up-regulation of COX-2. Apoptosis was also prevented by inhibitors of the prostaglandin uptake transporter PGT, which indicated that iPGE2 contributes to hypoxia-induced apoptosis (on the contrary, hypoxia/reoxygenation-induced PTC death was exclusively due to extracellular PGE2). Thus, iPGE2 is a new actor in the pathogenesis of hypoxia-induced tubular injury and PGT might be a new therapeutic target for the prevention of hypoxia-dependent lesions in renal diseases.
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