2024-03-29T11:54:35Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2184122021-12-28T15:38:36Zcom_10261_79com_10261_1col_10261_332
Bartosova, Maria
Herzog, Rebecca
Ridinger, David
Levai, Eszter
Jenei, Hanna
Zhang, Conghui
González-Mateo, Guadalupe
Marinovic, Iva
Hackert, Thilo
Bestvater, Felix
Hausmann, Michael
López Cabrera, Manuel
Kratochwill, Klaus
Zarogiannis, Sotirios G.
Schmitt, Claus Peter
2020-08-21T13:51:33Z
2020-08-21T13:51:33Z
2020-08-13
Biomolecules 10(8): 1178 (2020)
http://hdl.handle.net/10261/218412
10.3390/biom10081178
2218-273X
http://dx.doi.org/10.13039/100005156
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100001659
32823646
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.
http://creativecommons.org/licenses/by/4.0/
openAccess
peritoneal dialysis
tight junctions
paracellular transport
Alanyl-glutamine
Alanyl-glutamine restores tight junction organization after disruption by a conventional peritoneal dialysis fluid
artículo