Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid

Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) ecacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein los...

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Autores: Bartosova, Maria, Herzog, Rebecca, Ridinger, David, Levai, Eszter, Jenei, Hanna, Zhang, Conghui, González Mateo, Guadalupe T, Marinovic, Iva, Hackert, Thilo, Bestvater, Felix, López-Cabrera, Manuel, Kratochwill, Klaus, Zarogiannis, Sotirios G., Schmitt, Claus Peter
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/233800
Acceso en línea:http://hdl.handle.net/10261/233800
Access Level:acceso abierto
Palabra clave:Peritoneal dialysis
Tight junctions
Paracellular transport
Alanyl-glutamine
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spelling Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis FluidBartosova, MariaHerzog, RebeccaRidinger, DavidLevai, EszterJenei, HannaZhang, ConghuiGonzález Mateo, Guadalupe TMarinovic, IvaHackert, ThiloBestvater, FelixLópez-Cabrera, ManuelKratochwill, KlausZarogiannis, Sotirios G.Schmitt, Claus PeterPeritoneal dialysisTight junctionsParacellular transportAlanyl-glutamineUnderstanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) ecacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified byWestern blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/233800reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3390/biom10081178Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2338002026-05-22T06:33:51Z
dc.title.none.fl_str_mv Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
title Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
spellingShingle Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
Bartosova, Maria
Peritoneal dialysis
Tight junctions
Paracellular transport
Alanyl-glutamine
title_short Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
title_full Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
title_fullStr Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
title_full_unstemmed Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
title_sort Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid
dc.creator.none.fl_str_mv Bartosova, Maria
Herzog, Rebecca
Ridinger, David
Levai, Eszter
Jenei, Hanna
Zhang, Conghui
González Mateo, Guadalupe T
Marinovic, Iva
Hackert, Thilo
Bestvater, Felix
López-Cabrera, Manuel
Kratochwill, Klaus
Zarogiannis, Sotirios G.
Schmitt, Claus Peter
author Bartosova, Maria
author_facet Bartosova, Maria
Herzog, Rebecca
Ridinger, David
Levai, Eszter
Jenei, Hanna
Zhang, Conghui
González Mateo, Guadalupe T
Marinovic, Iva
Hackert, Thilo
Bestvater, Felix
López-Cabrera, Manuel
Kratochwill, Klaus
Zarogiannis, Sotirios G.
Schmitt, Claus Peter
author_role author
author2 Herzog, Rebecca
Ridinger, David
Levai, Eszter
Jenei, Hanna
Zhang, Conghui
González Mateo, Guadalupe T
Marinovic, Iva
Hackert, Thilo
Bestvater, Felix
López-Cabrera, Manuel
Kratochwill, Klaus
Zarogiannis, Sotirios G.
Schmitt, Claus Peter
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Peritoneal dialysis
Tight junctions
Paracellular transport
Alanyl-glutamine
topic Peritoneal dialysis
Tight junctions
Paracellular transport
Alanyl-glutamine
description Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) ecacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified byWestern blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/233800
url http://hdl.handle.net/10261/233800
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3390/biom10081178
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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