Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease.
Background: Chronic kidney disease (CKD) impairs intestinal barrier function which leads to endotoxemia and systemic inflammation. We have found depletion of intestinal epithelial tight junction (TJ) proteins in animals with CKD. We further showed that addition of end-stage renal disease patients' p...
| Publicado en: | American Journal of Nephrology Vol. 37; no. 1; pp. 1 - 7 |
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| Autores principales: | , , |
| Formato: | research Journal Article |
| Publicado: |
Karger AG
Feb2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104316129&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104316129 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02508095 8BL jtl: American Journal of Nephrology issn: 02508095 maglogo: N pubinfo: dt: Feb2013 vid: 37 iid: 1 pid: 2485 pub: Karger AG artinfo: ui: 104316129 NLM23258127 2012007573 10.1159/000345969 NLM23258127 PMC3686571 104316129 ppf: 1 ppct: 6 formats: tig: atl: Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease. aug: au: Vaziri, Nosratola D Yuan, Jun Norris, Keith affil: Division of Nephrology and Hypertension, University of California, Irvine, Calif., USA. sug: subj: Epithelial Cells Metabolism Renal Insufficiency Metabolism Urea Metabolism Urease Metabolism Cells Electric Impedance Human Hydrogen-Ion Concentration Cell Membrane Metabolism ab: Background: Chronic kidney disease (CKD) impairs intestinal barrier function which leads to endotoxemia and systemic inflammation. We have found depletion of intestinal epithelial tight junction (TJ) proteins in animals with CKD. We further showed that addition of end-stage renal disease patients' plasma to the culture medium provokes a marked drop in transepithelial electrical resistance (TER) and depletion of TJ proteins in cultured human enterocytes. These effects were less severe with post- than with prehemodialysis plasma, suggesting a role of dialyzable agent(s). This study tested the hypothesis that intestinal barrier dysfunction in uremia may be due to diffusion of urea into the gut and its conversion to ammonia by microbial urease.Methods: Human enterocytes (T84 cells) were seeded on Transwell plates and utilized when TER exceeded 1,000 mΩ·cm(2) to ensure full polarization and TJ formation. Confluent cells were then incubated for 24 h in media containing 0, 42 or 74 mg/dl urea or urea plus urease to simulate presence of microbial flora.Results: At clinically relevant concentrations, urea caused a concentration-dependent fall in TER and the key TJ proteins claudin-1, occludin and zonula occludens 1. The effects of urea were dramatically amplified by urease causing cell detachment, dissipation of TER, and massive loss of TJ proteins.Conclusions: Uremia-induced disruption of intestinal TJ and barrier function is, in part, mediated by urea which is generally considered to be a nontoxic retained metabolite. These findings reveal a novel mechanism for a salutary effect of urea-lowering strategies, e.g. low-protein diet and longer and more frequent dialysis regimens in advanced CKD. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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