Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis
- PMID: 9922310
- DOI: 10.1016/s0016-5085(99)70126-5
Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis
Abstract
Background & aims: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis (UC) was performed.
Methods: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy.
Results: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 omega3. cm2, which in conventional analysis is masked by an increase in subepithelial resistance from 14 +/- 1 to 36 +/- 3 omega3. cm2 caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 +/- 0.25 to 4.76 +/- 0.47 at the surface and from 7.26 +/- 0.31 to 5.46 +/- 0.37 in the crypts.
Conclusions: The inflamed colonic mucosa in UC has an impaired barrier function that is much more pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC.
Similar articles
-
Decreased Expression of Cystathionine β-Synthase Exacerbates Intestinal Barrier Injury in Ulcerative Colitis.J Crohns Colitis. 2019 Aug 14;13(8):1067-1080. doi: 10.1093/ecco-jcc/jjz027. J Crohns Colitis. 2019. PMID: 30722010
-
Therapeutic options to modulate barrier defects in inflammatory bowel disease.Dig Dis. 2009;27(4):450-4. doi: 10.1159/000233283. Epub 2009 Nov 4. Dig Dis. 2009. PMID: 19897959 Review.
-
Epithelial tight junctions in intestinal inflammation.Ann N Y Acad Sci. 2009 May;1165:294-300. doi: 10.1111/j.1749-6632.2009.04062.x. Ann N Y Acad Sci. 2009. PMID: 19538319 Review.
-
Mechanisms of diarrhea in collagenous colitis.Gastroenterology. 2002 Aug;123(2):433-43. doi: 10.1053/gast.2002.34784. Gastroenterology. 2002. PMID: 12145796
-
Epithelial barrier and transport function of the colon in ulcerative colitis.Ann N Y Acad Sci. 2000;915:312-26. doi: 10.1111/j.1749-6632.2000.tb05259.x. Ann N Y Acad Sci. 2000. PMID: 11193594 No abstract available.
Cited by
-
The barrier-protective effect of β-eudesmol against type 2-inflammatory cytokine-induced tight junction disassembly in airway epithelial cells.PLoS One. 2024 Apr 30;19(4):e0302851. doi: 10.1371/journal.pone.0302851. eCollection 2024. PLoS One. 2024. PMID: 38687777 Free PMC article.
-
Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice.Nat Commun. 2024 Mar 26;15(1):2645. doi: 10.1038/s41467-024-46983-5. Nat Commun. 2024. PMID: 38531874 Free PMC article.
-
Adenosine in Intestinal Epithelial Barrier Function.Cells. 2024 Feb 23;13(5):381. doi: 10.3390/cells13050381. Cells. 2024. PMID: 38474346 Free PMC article. Review.
-
MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C.J Cell Sci. 2024 Mar 1;137(5):jcs261468. doi: 10.1242/jcs.261468. Epub 2024 Mar 13. J Cell Sci. 2024. PMID: 38345099 Free PMC article.
-
Trichinella spiralis cathepsin L damages the tight junctions of intestinal epithelial cells and mediates larval invasion.PLoS Negl Trop Dis. 2023 Dec 4;17(12):e0011816. doi: 10.1371/journal.pntd.0011816. eCollection 2023 Dec. PLoS Negl Trop Dis. 2023. PMID: 38048314 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical