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Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis: Are These Potential
Sebastian Kjærgaard1, Morten M B Damm1, Joan Chang2
1Digestive Disease Center, Bispebjerg Hospital, 2400 Copenhagen, Denmark.
International Journal of Molecular Sciences
|March 14, 2020
Summary
Even in remission, ulcerative colitis (UC) patients show molecular and functional gut barrier defects. These findings suggest current remission standards may need revision to include mucosal healing markers.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Endoscopic mucosal healing is the standard for ulcerative colitis (UC) remission.
- Histologic normalization may better predict relapse risk in UC.
- Molecular and functional aspects of mucosal healing in quiescent UC require further investigation.
Purpose of the Study:
- To investigate molecular and functional mucosal healing in quiescent UC patients.
- To compare UC patients with healthy controls at the molecular level.
- To assess the correlation between molecular changes and functional barrier properties.
Main Methods:
- Endoscopic biopsies from 33 quiescent UC patients and 17 controls.
- Assessment of histology (Geboes score), protein, and mRNA levels of tight junction proteins and cyclo-oxygenase enzymes.
- Functional assessment of mucosal ion transport using Ussing chambers and short-circuit current (SCC) measurements.
Main Results:
- UC patients exhibited chronic inflammation despite endoscopic remission.
- Reduced claudin-4 protein and upregulated claudin-2/claudin-4 mRNA levels were observed in UC patients.
- COX-2 inhibition caused a greater decrease in SCC in UC patients, indicating altered functional barrier properties.
Conclusions:
- Quiescent UC patients display molecular and functional abnormalities in their mucosal barrier.
- Current remission standards for UC may not fully capture mucosal healing.
- Further research into molecular signatures is recommended for refining UC remission criteria.
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