The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR

Detalhes bibliográficos
Autor(a) principal: Roxo-Rosa, Mónica
Data de Publicação: 2015
Outros Autores: Jacinto, Raquel, Sampaio, Pedro, Lopes, Susana Santos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/21522
Resumo: Work supported by Fundacao para a Ciencia e a Tecnologia [FCT-ANR/BEX-BID/0153/2012 research grant], including funding for M.R.-R. and P.S. S.S.L. has a FCT-Investigator contract and R.J. a PhD fellowship [PD/BD/52420/2013].
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spelling The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTRMOUSE MODELCL-SECRETIONADPKDCALCIUMCystic fibrosis transmembrane conductance regulator (CFTR)FIBROSISKIDNEY-DISEASEKupffer's vesicle (KV)Polycystin-2CELL-PROLIFERATIONAutosomal dominant polycystic kidney disease (ADPKD)EPITHELIAL-CELLSZebrafishPRIMARY CILIUMRENAL CYST GROWTHAutosomal dominant polycystic kidney disease (ADPKD)Cystic fibrosis transmembrane conductance regulator (CFTR)Kupffer's vesicle (KV)Polycystin-2ZebrafishQH301 BiologyWork supported by Fundacao para a Ciencia e a Tecnologia [FCT-ANR/BEX-BID/0153/2012 research grant], including funding for M.R.-R. and P.S. S.S.L. has a FCT-Investigator contract and R.J. a PhD fellowship [PD/BD/52420/2013].In autosomal dominant polycystic kidney disease (ADPKD), cyst inflation and continuous enlargement are associated with marked transepithelial ion and fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR). Indeed, the inhibition or degradation of CFTR prevents the fluid accumulation within cysts. The in vivo mechanisms by which the lack of Polycystin-2 leads to CFTR stimulation are an outstanding challenge in ADPKD research and may bring important biomarkers for the disease. However, hampering their study, the available ADPKD in vitro cellular models lack the three-dimensional architecture of renal cysts and the ADPKD mouse models offer limited access for live-imaging experiments in embryonic kidneys. Here, we tested the zebrafish Kupffer's vesicle (KV) as an alternative model-organ. KV is a fluid-filled vesicular organ, lined by epithelial cells that express both CFTR and Polycystin-2 endogenously, being each of them easily knocked-down. Our data on the intracellular distribution of Polycystin-2 support its involvement in the KV fluid-flow induced Ca2+-signalling. Mirroring kidney cysts, the KV lumen inflation is dependent on CFTR activity and, as we clearly show, the knockdown of Polycystin-2 results in larger KV lumens through overstimulation of CFTR. In conclusion, we propose the zebrafish KV as a model organ to study the renal cyst inflation. Favouring its use, KV volume can be easily determined by in vivo imaging offering a live readout for screening compounds and genes that may prevent cyst enlargement through CFTR inhibition.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNRoxo-Rosa, MónicaJacinto, RaquelSampaio, PedroLopes, Susana Santos2017-06-09T22:02:15Z2015-01-012015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/21522eng2046-6390PURE: 501890https://doi.org/10.1242/bio.014076info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:08:17Zoai:run.unl.pt:10362/21522Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:26:50.355039Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
title The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
spellingShingle The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
Roxo-Rosa, Mónica
MOUSE MODEL
CL-SECRETION
ADPKD
CALCIUM
Cystic fibrosis transmembrane conductance regulator (CFTR)
FIBROSIS
KIDNEY-DISEASE
Kupffer's vesicle (KV)
Polycystin-2
CELL-PROLIFERATION
Autosomal dominant polycystic kidney disease (ADPKD)
EPITHELIAL-CELLS
Zebrafish
PRIMARY CILIUM
RENAL CYST GROWTH
Autosomal dominant polycystic kidney disease (ADPKD)
Cystic fibrosis transmembrane conductance regulator (CFTR)
Kupffer's vesicle (KV)
Polycystin-2
Zebrafish
QH301 Biology
title_short The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
title_full The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
title_fullStr The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
title_full_unstemmed The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
title_sort The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR
author Roxo-Rosa, Mónica
author_facet Roxo-Rosa, Mónica
Jacinto, Raquel
Sampaio, Pedro
Lopes, Susana Santos
author_role author
author2 Jacinto, Raquel
Sampaio, Pedro
Lopes, Susana Santos
author2_role author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Roxo-Rosa, Mónica
Jacinto, Raquel
Sampaio, Pedro
Lopes, Susana Santos
dc.subject.por.fl_str_mv MOUSE MODEL
CL-SECRETION
ADPKD
CALCIUM
Cystic fibrosis transmembrane conductance regulator (CFTR)
FIBROSIS
KIDNEY-DISEASE
Kupffer's vesicle (KV)
Polycystin-2
CELL-PROLIFERATION
Autosomal dominant polycystic kidney disease (ADPKD)
EPITHELIAL-CELLS
Zebrafish
PRIMARY CILIUM
RENAL CYST GROWTH
Autosomal dominant polycystic kidney disease (ADPKD)
Cystic fibrosis transmembrane conductance regulator (CFTR)
Kupffer's vesicle (KV)
Polycystin-2
Zebrafish
QH301 Biology
topic MOUSE MODEL
CL-SECRETION
ADPKD
CALCIUM
Cystic fibrosis transmembrane conductance regulator (CFTR)
FIBROSIS
KIDNEY-DISEASE
Kupffer's vesicle (KV)
Polycystin-2
CELL-PROLIFERATION
Autosomal dominant polycystic kidney disease (ADPKD)
EPITHELIAL-CELLS
Zebrafish
PRIMARY CILIUM
RENAL CYST GROWTH
Autosomal dominant polycystic kidney disease (ADPKD)
Cystic fibrosis transmembrane conductance regulator (CFTR)
Kupffer's vesicle (KV)
Polycystin-2
Zebrafish
QH301 Biology
description Work supported by Fundacao para a Ciencia e a Tecnologia [FCT-ANR/BEX-BID/0153/2012 research grant], including funding for M.R.-R. and P.S. S.S.L. has a FCT-Investigator contract and R.J. a PhD fellowship [PD/BD/52420/2013].
publishDate 2015
dc.date.none.fl_str_mv 2015-01-01
2015-01-01T00:00:00Z
2017-06-09T22:02:15Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/21522
url http://hdl.handle.net/10362/21522
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2046-6390
PURE: 501890
https://doi.org/10.1242/bio.014076
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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