#5837 MOLECULAR AND FUNCTIONAL CHARACTERIZATION OF THE PERITONEAL MESOTHELIAL AND ENDOTHELIAL CELL BARRIER

Abstract Background and Aims Solute transport across cellular levels is mediated by paracellular transcellular pores, channels carriers. Knowledge on their cell specific expression, regulation function in peritoneal dialysis (PD) limited. Method Polarized primary (HPMC) immortalized human mesothelial (MeT-5A), microvascular (HCMEC) umbilical vein endothelial (HUVEC) cells underwent RNA sequencing gene enrichment analysis. Key findings were confirmed western blotting (WB), confocal single molecule localization microscopy (SMLM). Arteriolar transcriptome proteome datasets of non-CKD, CKD5 PD children (n = 6/group) targeted pathways transporter proteins quantified parietal peritoneum 20–30/group) related to rates available 23 children. Barrier was studied vitro (transepithelial electrical resistance, TER, molecular weight dependent flux), ex vivo vivo. Results Junction, transmembrane transcytotic expression highly type protein level. Sealing Claudin (CLDN)1 only expressed cells, sealing CLDN5 cells. TER which reflects functional junction status, 50% lower HCMEC compared HUVEC the two lines; 4- 10-kDa dextran permeability higher HCMEC. At nanoscale, SMLM yielded highest distance molecules different spatial organisation, reflecting low TER. In sheep peritoneum, removal mesothelium abolished tissue mice, short-term LPS exposure modify resulted faster transperitoneal 70-kDa transport, suggesting a barrier mesothelium. total surface area per section age dependently 1.5- 2-fold than respective area, further increased with double-chamber fluid, due major hypervascularisation. Tight CLDN-1 -5, -15, ZO-1, occludin tricellulin, ENaC, PIT1, SGLT1 detected arteriolar CKD CLDN-2 -3 more abundant non-CKD controls, patients had CLDN-2, claudin-3 ENaC. D/P creatinine D/D0 glucose correlated CLDN-4 are pore forming junctions, for PIT-1, sodium/phosphate co-transporter. Conclusion We provide first in-depth analysis determinants solute transport. The pattern differs substantially. Disruption layer increases absorption rate. status modified PD, associated dialytic function. These represent promising target therapeutic intervention.