P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin
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...
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MDPI AG
2020-01-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/2/62 |
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| author | Shih-Chieh Chen Shin-Yin Huang Chia-Chun Wu Chiung-Fang Hsu |
| author_facet | Shih-Chieh Chen Shin-Yin Huang Chia-Chun Wu Chiung-Fang Hsu |
| author_sort | Shih-Chieh Chen |
| collection | DOAJ |
| description | 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 (0.1−0.2 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. |
| first_indexed | 2024-04-13T08:05:40Z |
| format | Article |
| id | doaj.art-5755cbc8e22e4b58906563fa5e53b0f2 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-13T08:05:40Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-5755cbc8e22e4b58906563fa5e53b0f22022-12-22T02:55:10ZengMDPI AGToxins2072-66512020-01-011226210.3390/toxins12020062toxins12020062P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-CadherinShih-Chieh Chen0Shin-Yin Huang1Chia-Chun Wu2Chiung-Fang Hsu3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Anatomy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708 TaiwanDepartment of Nephrology, Chi Mei Medical Center, Tainan 71004, TaiwanDepartment of Anatomy, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708 TaiwanThe 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 (0.1−0.2 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.https://www.mdpi.com/2072-6651/12/2/62p-cresylsulfateendothelial permeabilityve-cadherinchronic kidney diseasesrc kinaseendothelial dysfunction |
| spellingShingle | Shih-Chieh Chen Shin-Yin Huang Chia-Chun Wu Chiung-Fang Hsu P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin Toxins p-cresylsulfate endothelial permeability ve-cadherin chronic kidney disease src kinase endothelial dysfunction |
| title | P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin |
| title_full | P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin |
| title_fullStr | P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin |
| title_full_unstemmed | P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin |
| title_short | P-Cresylsulfate, the Protein-Bound Uremic Toxin, Increased Endothelial Permeability Partly Mediated by Src-Induced Phosphorylation of VE-Cadherin |
| title_sort | p cresylsulfate the protein bound uremic toxin increased endothelial permeability partly mediated by src induced phosphorylation of ve cadherin |
| topic | p-cresylsulfate endothelial permeability ve-cadherin chronic kidney disease src kinase endothelial dysfunction |
| url | https://www.mdpi.com/2072-6651/12/2/62 |
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