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

Biomolecules

Rebecca Herzog¹  Klaus Kratochwill¹  SotiriosG. Zarogiannis²  Conghui Zhang²  Iva Marinovic²  Eszter Levai²  Hanna Jenei²  Maria Bartosova²  ClausPeter Schmitt²  Thilo Hackert³  Felix Bestvater⁴  GuadalupeT. González Mateo⁵  Manuel López Cabrera⁵  David Ridinger⁶  Michael Hausmann⁶ 

[1] Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria;Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany;General, Visceral and Transplantation Surgery, Heidelberg University, 69120 Heidelberg, Germany;German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany;Immunology and Cellular Biology Department, Molecular Biology Centre Severo Ochoa, 28049 Madrid, Spain;Kirchhoff Institute for Physics, Heidelberg University, 69120 Heidelberg, Germany;

关键词: peritoneal dialysis;    tight junctions;    paracellular transport;    alanyl-glutamine;   

DOI  :  10.3390/biom10081178

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown