Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation

Scientific Reports
Vineeta KhareChristoph Gasche

Abstract

Disruption of mucosal structure and barrier function contribute to the pathogenesis of inflammatory bowel disease (IBD). Efficacy of therapy in IBD is based on endoscopic mucosal healing, which occurs by a dynamic interplay of epithelial cell regeneration, migration and differentiation. Both mesalamine (5-ASA) and azathioprine (AZTP) promote this process through mechanisms not clearly understood. We examined molecular pathways implicated in epithelial barrier function that were altered by 5-ASA and AZTP. Paracellular permeability induced by inflammatory mediators was mitigated by both compounds through restoration of cellular anchoring complexes. 5-ASA and AZTP induced rearrangement and membranous localization of junctional proteins and modulated genes involved in tight junctions. Intestinal organoids from wildtype-mice treated with TNF-α and IL-10- deficient-mice displayed impaired epithelial barrier with loss of membranous E-cadherin and reduced Desmoglein-2 expression. These effects were counteracted by 5-ASA and AZTP. Unlike AZTP that exhibited antiproliferative effects, 5-ASA promoted wound healing in colon epithelial cells. Both affected cellular senescence, cell cycle distribution and restricted cells in G1 or S phase wi...Continue Reading

References

Sep 1, 1985·The Journal of Clinical Investigation·M J WelshR M Husted
Feb 1, 1984·The American Journal of Physiology·K DharmsathaphornH Masui
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·A NusratJ L Madara
Jun 1, 1994·Alimentary Pharmacology & Therapeutics·L A ChristensenS N Rasmussen
Feb 1, 1996·The Journal of Cell Biology·A K RajasekaranE Rodriguez-Boulan
Apr 17, 2003·The Journal of Clinical Investigation·Imke TiedeMarkus F Neurath
Apr 3, 2004·Inflammatory Bowel Diseases·Renata D'IncàGiacomo Carlo Sturniolo
Oct 24, 2007·Biochimica Et Biophysica Acta·Lorenza González-MariscalDavid Chamorro
Dec 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian A BabbinAsma Nusrat
Nov 17, 2009·Nature Genetics·UNKNOWN UK IBD Genetics ConsortiumDavid P Strachan
Aug 21, 2010·Inflammatory Bowel Diseases·Sa'ad Y Salim, Johan D Söderholm
Dec 4, 2010·Biochimica Et Biophysica Acta·Mehmet CoskunOle Haagen Nielsen
May 3, 2011·Gastroenterology·Thomas A Ullman, Steven H Itzkowitz
Jun 17, 2011·Nature·Bernard KhorRamnik J Xavier
Aug 30, 2011·Methods in Molecular Biology·Rino P DonatoBarry C Powell
Nov 30, 2011·Best Practice & Research. Clinical Gastroenterology·Christoph Campregher, Christoph Gasche
Jun 27, 2012·Annals of the New York Academy of Sciences·Kevin E Cunningham, Jerrold R Turner
Nov 14, 2012·Biochemical Pharmacology·Vineeta KhareChristoph Gasche
Oct 15, 2013·The American Journal of Pathology·Rana Al-SadiThomas Y Ma
Mar 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Goran MarinkovićVivian de Waard
May 9, 2014·Gut·Kyle DammannChristoph Gasche
Jun 24, 2014·Nature Reviews. Molecular Cell Biology·Daniel Muñoz-Espín, Manuel Serrano
Jan 9, 2015·Inflammatory Bowel Diseases·Vineeta KhareChristoph Gasche
Mar 21, 2017·Mediators of Inflammation·Jan BilskiTomasz Brzozowski
Dec 1, 2017·Nature Reviews. Gastroenterology & Hepatology·Nina FreyMichael Bitzer
Jan 31, 2018·Molecular Cancer Research : MCR·Adrian FrickChristoph Gasche

❮ Previous
Next ❯

Citations

Nov 19, 2019·Frontiers in Pharmacology·Peeraphong LertnimitphunHongxi Xu
Jan 10, 2021·Pharmaceutics·Daniela Placha, Josef Jampilek
Nov 16, 2020·Cellular and Molecular Gastroenterology and Hepatology·Adrian FrickChristoph Gasche
Feb 22, 2021·Cellular and Molecular Gastroenterology and Hepatology·Sweta GhoshVenkatakrishna Rao Jala
Mar 6, 2021·Scientific Reports·Rayko EvstatievChristoph Gasche
Apr 28, 2021·Inflammatory Bowel Diseases·Adam S Faye, Jean-Frederic Colombel
Jul 17, 2021·Cellular and Molecular Gastroenterology and Hepatology·Huong D NguyenAndrew W Stadnyk
Dec 21, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Emilie BersuderIsabelle Gross

❮ Previous
Next ❯

Methods Mentioned

BETA
IEC
biopsies
PCR
nuclear translocation
flow cytometry
fluorescence assay

Software Mentioned

ImageJ
Cellsens dimension
GraphPad Prism
Adobe Photoshop
Pathway

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.