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The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients
The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colon...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053841/ https://www.ncbi.nlm.nih.gov/pubmed/36986672 http://dx.doi.org/10.3390/pharmaceutics15030811 |
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author | Park, Young Su Kang, Sang Bum Marchelletta, Ronald R. Penrose, Harrison M. Ruiter-Visser, Roos Jung, Barbara Docherty, Michael J. Boland, Brigid S. Sandborn, William J. McCole, Declan F. |
author_facet | Park, Young Su Kang, Sang Bum Marchelletta, Ronald R. Penrose, Harrison M. Ruiter-Visser, Roos Jung, Barbara Docherty, Michael J. Boland, Brigid S. Sandborn, William J. McCole, Declan F. |
author_sort | Park, Young Su |
collection | PubMed |
description | The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colonic biopsies from Crohn’s disease (CD) and ulcerative colitis (UC) patients. Sigmoid colon biopsies from healthy subjects, CD and UC patients in remission, and CD patients with active disease were mounted in Ussing chambers. Tissues were treated with lubiprostone or vehicle to determine the effects on transepithelial electrical resistance (TER), FITC-dextran 4kD (FD4) permeability, and electrogenic ion transport responses to forskolin and carbachol. Localization of the tight junction protein, occludin, was determined by immunofluorescence. Lubiprostone significantly increased ion transport across control, CD and UC remission biopsies but not active CD. Lubiprostone selectively improved TER in both CD remission and active disease biopsies but not in control or UC biopsies. The improved TER was associated with increased membrane localization of occludin. Lubiprostone selectively improved barrier properties of biopsies from CD patients vs. UC and independent of an ion transport response. These data indicate that lubiprostone has potential efficacy in improving mucosal integrity in Crohn’s disease. |
format | Online Article Text |
id | pubmed-10053841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100538412023-03-30 The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients Park, Young Su Kang, Sang Bum Marchelletta, Ronald R. Penrose, Harrison M. Ruiter-Visser, Roos Jung, Barbara Docherty, Michael J. Boland, Brigid S. Sandborn, William J. McCole, Declan F. Pharmaceutics Article The prostone analog, lubiprostone, is approved to manage constipation-predominant irritable bowel syndrome. Lubiprostone also protects intestinal mucosal barrier function in animal models of colitis. The aim of this study was to determine if lubiprostone improves barrier properties in isolated colonic biopsies from Crohn’s disease (CD) and ulcerative colitis (UC) patients. Sigmoid colon biopsies from healthy subjects, CD and UC patients in remission, and CD patients with active disease were mounted in Ussing chambers. Tissues were treated with lubiprostone or vehicle to determine the effects on transepithelial electrical resistance (TER), FITC-dextran 4kD (FD4) permeability, and electrogenic ion transport responses to forskolin and carbachol. Localization of the tight junction protein, occludin, was determined by immunofluorescence. Lubiprostone significantly increased ion transport across control, CD and UC remission biopsies but not active CD. Lubiprostone selectively improved TER in both CD remission and active disease biopsies but not in control or UC biopsies. The improved TER was associated with increased membrane localization of occludin. Lubiprostone selectively improved barrier properties of biopsies from CD patients vs. UC and independent of an ion transport response. These data indicate that lubiprostone has potential efficacy in improving mucosal integrity in Crohn’s disease. MDPI 2023-03-02 /pmc/articles/PMC10053841/ /pubmed/36986672 http://dx.doi.org/10.3390/pharmaceutics15030811 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Park, Young Su Kang, Sang Bum Marchelletta, Ronald R. Penrose, Harrison M. Ruiter-Visser, Roos Jung, Barbara Docherty, Michael J. Boland, Brigid S. Sandborn, William J. McCole, Declan F. The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
title | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
title_full | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
title_fullStr | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
title_full_unstemmed | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
title_short | The ClC-2 Chloride Channel Activator, Lubiprostone, Improves Intestinal Barrier Function in Biopsies from Crohn’s Disease but Not Ulcerative Colitis Patients |
title_sort | clc-2 chloride channel activator, lubiprostone, improves intestinal barrier function in biopsies from crohn’s disease but not ulcerative colitis patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053841/ https://www.ncbi.nlm.nih.gov/pubmed/36986672 http://dx.doi.org/10.3390/pharmaceutics15030811 |
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