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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) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein...

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Main Authors: Bartosova, Maria (Author) , Herzog, Rebecca (Author) , Ridinger, David (Author) , Levai, Eszter (Author) , Jenei, Hanna (Author) , Zhang, Conghui (Author) , González Mateo, Guadalupe T. (Author) , Marinovic, Iva (Author) , Hackert, Thilo (Author) , Bestvater, Felix (Author) , Hausmann, Michael (Author) , López Cabrera, Manuel (Author) , Kratochwill, Klaus (Author) , Zarogiannis, Sotirios G. (Author) , Schmitt, Claus P. (Author)
Format: Article (Journal)
Language:English
Published: 13 August 2020
In: Biomolecules
Year: 2020, Volume: 10, Issue: 8
ISSN:2218-273X
DOI:10.3390/biom10081178
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/biom10081178
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2218-273X/10/8/1178
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Author Notes:Maria Bartosova, Rebecca Herzog, David Ridinger, Eszter Levai, Hanna Jenei, Conghui Zhang, Guadalupe T. González Mateo, Iva Marinovic, Thilo Hackert, Felix Bestvater, Michael Hausmann, Manuel López Cabrera, Klaus Kratochwill, Sotirios G. Zarogiannis and Claus Peter Schmitt
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Summary:Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy 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 by Western 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.
Item Description:Gesehen am 12.11.2020
Physical Description:Online Resource
ISSN:2218-273X
DOI:10.3390/biom10081178

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