{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:36:43Z","timestamp":1793241403970,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The goal of our study was to investigate the impact of p-cresylsulfate (PCS) on the barrier integrity in human umbilical vein endothelial cell (HUVEC) monolayers and the renal artery of chronic kidney disease (CKD) patients. We measured changes in the transendothelial electrical resistance (TEER) of HUVEC monolayers treated with PCS (0.1\u20130.2 mM) similar to serum levels of CKD patients. A PCS dose (0.2 mM) significantly decreased TEER over a 48-h period. Both PCS doses (0.1 and 0.2 mM) significantly decreased TEER over a 72-h period. Inter-endothelial gaps were observed in HUVECs following 48 h of PCS treatment by immunofluorescence microscopy. We also determined whether PCS induced the phosphorylation of VE-cadherin at tyrosine 658 (Y658) mediated by the phosphorylation of Src. Phosphorylated VE-cadherin (Y658) and phosphorylated Src levels were significantly higher when the cells were treated with 0.1 and 0.2 mM PCS, respectively, compared to the controls. The endothelial barrier dysfunction in the arterial intima in CKD patients was evaluated by endothelial leakage of immunoglobulin G (IgG). Increased endothelial leakage of IgG was related to the declining kidney function in CKD patients. Increased endothelial permeability induced by uremic toxins, including PCS, suggests that uremic toxins induce endothelial barrier dysfunction in CKD patients and Src-mediated phosphorylation of VE-cadherin is involved in increased endothelial permeability induced by PCS exposure.<\/jats:p>","DOI":"10.3390\/toxins12020062","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T07:41:11Z","timestamp":1580110871000},"page":"62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7414-4734","authenticated-orcid":false,"given":"Shih-Chieh","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Anatomy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708 Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Yin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9788-2948","authenticated-orcid":false,"given":"Chia-Chun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Chi Mei Medical Center, Tainan 71004, Taiwan"},{"name":"Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiung-Fang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1681\/ASN.2005030310","article-title":"Removal of P-cresol sulfate by hemodialysis","volume":"16","author":"Martinez","year":"2005","journal-title":"J. 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