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Zebrafish model as a screen to prevent cyst inflation in autosomal dominant polycystic kidney disease

2021-08-02Artigo científico Acesso aberto
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dc.contributor.authorOliveira, Inês
dc.contributor.authorJacinto, Raquel
dc.contributor.authorPestana, Sara
dc.contributor.authorPestana, Sara
dc.contributor.authorNolasco, Fernando
dc.contributor.authorCalado, Joaquim
dc.contributor.authorLopes, Susana Santos
dc.contributor.authorRoxo-Rosa, Mónica
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentre for Toxicogenomics and Human Health (ToxOmics)
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2021-09-24T02:24:55Z
dc.date.available2021-09-24T02:24:55Z
dc.date.issued2021-08-02
dc.descriptionFunding Information: Funding: This work was supported by Sociedade Portuguesa de Nefrologia, iNOVA4Health-UID/Multi/04462/2013 (a program financially supported by Fundação para a Ciência e Tecnolo-gia (FCT)/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement) and FCT-ANR/BEX-BID/0153/2012 and PTDC/BEX-BID/1411/2014 research grants. M.R.R. was supported by national funds through FCT, first with an iNOVA post-doctoral fellowship and, more recently, with a contract in the context of the celebration of the program contract foreseen in the numbers 4, 5, and 6 of article 23.◦ of D.L. no. 57/2016 of 29 August, as amended by Law no. 57/2017 of 19 July. S.S.L. had a FCT-Investigator contract, followed by NOVA NMS contracts and, at the moment, a FCT CEEC (Concurso Estímulo ao Emprego Científico) contract, as principal investigator. This article is supported by the LYSOCIL project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 811087. Zebrafish used as an animal model were reproduced and maintained in the CEDOC Fish Facility, with the support from the research infrastructure Congento, co-financed by Lisboa Regional Operational Programme (Lisboa2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and FCT under the project LISBOA-01-0145-FEDER-022170. Funding Information: This work was supported by Sociedade Portuguesa de Nefrologia, iNOVA4Health-UID/Multi/04462/2013 (a program financially supported by Funda??o para a Ci?ncia e Tecnolo-gia (FCT)/Minist?rio da Educa??o e Ci?ncia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement) and FCT-ANR/BEX-BID/0153/2012 and PTDC/BEX-BID/1411/2014 research grants. M.R.R. was supported by national funds through FCT, first with an iNOVA post-doctoral fellowship and, more recently, with a contract in the context of the celebration of the program contract foreseen in the numbers 4, 5, and 6 of article 23.? of D.L. no. 57/2016 of 29 August, as amended by Law no. 57/2017 of 19 July. S.S.L. had a FCT-Investigator contract, followed by NOVA NMS contracts and, at the moment, a FCT CEEC (Concurso Est?mulo ao Emprego Cient?fico) contract, as principal investigator. This article is supported by the LYSOCIL project. This project has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No 811087. Zebrafish used as an animal model were reproduced and maintained in the CEDOC Fish Facility, with the support from the research infrastructure Congento, co-financed by Lisboa Regional Operational Programme (Lisboa2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and FCT under the project LISBOA-01-0145-FEDER-022170. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
dc.description.abstractIn autosomal dominant polycystic kidney disease (ADPKD), kidney cyst growth requires the recruitment of CFTR (cystic fibrosis transmembrane conductance regulator), the chloride channel that is defective in cystic fibrosis. We have been studying cyst inflation using the zebrafish Kupffer’s vesicle (KV) as model system because we previously demonstrated that knocking down polycystin 2 (PC2) induced a CFTR-mediated enlargement of the organ. We have now quantified the PC2 knock-down by showing that it causes a 73% reduction in the number of KV cilia expressing PC2. According to the literature, this is an essential event in kidney cystogenesis in ADPKD mice. Additionally, we demonstrated that the PC2 knockdown leads to a significant accumulation of CFTR-GFP at the apical region of the KV cells. Furthermore, we determined that KV enlargement is rescued by the injection of Xenopus pkd2 mRNA and by 100 µM tolvaptan treatment, the unique and approved pharmacologic approach for ADPKD management. We expected vasopressin V2 receptor antagonist to lower the cAMP levels of KV-lining cells and, thus, to inactivate CFTR. These findings further support the use of the KV as an in vivo model for screening compounds that may prevent cyst enlargement in this ciliopathy, through CFTR inhibition.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent3483149
dc.identifier.doi10.3390/ijms22169013
dc.identifier.issn1661-6596
dc.identifier.otherPURE: 33458999
dc.identifier.otherPURE UUID: ce0e3562-2dbb-4ae9-9120-06bac0fb9493
dc.identifier.otherScopus: 85113211470
dc.identifier.otherORCID: /0000-0002-1194-3392/work/100453707
dc.identifier.otherORCID: /0000-0002-7089-1975/work/100453738
dc.identifier.otherWOS: 000690632800001
dc.identifier.otherPubMed: 34445719
dc.identifier.urihttp://hdl.handle.net/10362/125091
dc.identifier.urlhttps://www.scopus.com/pages/publications/85113211470
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAutosomal dominant polycystic kidney disease (ADPKD)
dc.subjectCystic fibrosis transmembrane conductance regulator (CFTR)
dc.subjectKupffer’s vesicle (KV)
dc.subjectPolycystin-2 (PC2)
dc.subjectCatalysis
dc.subjectMolecular Biology
dc.subjectSpectroscopy
dc.subjectComputer Science Applications
dc.subjectPhysical and Theoretical Chemistry
dc.subjectOrganic Chemistry
dc.subjectInorganic Chemistry
dc.titleZebrafish model as a screen to prevent cyst inflation in autosomal dominant polycystic kidney diseaseen
dc.typejournal article
degois.publication.issue16
degois.publication.titleInternational Journal of Molecular Sciences
degois.publication.volume22
dspace.entity.typePublication
person.familyNameSilva Pestana
person.givenNameSara Filipa
person.identifier.ciencia-id651B-A763-ECF5
person.identifier.orcid0000-0002-0995-0040
rcaap.rightsopenAccess
relation.isAuthorOfPublicationa9c7ed87-f87d-4c87-8873-9055107f1f88
relation.isAuthorOfPublication.latestForDiscoverya9c7ed87-f87d-4c87-8873-9055107f1f88

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