Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis: Are These Potential Normalization Criteria?

Abstract

Mucosal healing determined by endoscopy is currently the remission standard for ulcerative colitis (UC). However, new criteria for remission are emerging, such as histologic normalization, which appears to correlate better to the risk of relapse. Here, we study mucosal healing on a molecular and functional level in quiescent UC. We obtained endoscopic biopsies from 33 quiescent UC patients and from 17 controls. Histology was assessed using Geboes score. Protein and mRNA levels were evaluated for the tight junction proteins claudin-2, claudin-4, occludin, and tricellulin, as well as Cl−/HCO3− exchanger DRA, and cyclo-oxygenase enzymes (COX-1, COX-2). The mucosal activity of COX-1 and COX-2 enzymes was assessed in modified Ussing chambers, measuring electrogenic ion transport (short-circuit current, SCC). Chronic inflammation was present in most UC patients. The protein level of claudin-4 was reduced, while mRNA-levels of claudin-2 and claudin-4 were upregulated in UC patients. Surprisingly, the mRNA level of COX-1 was downregulated, but was unaltered for COX-2. Basal ion transport was not affected, while COX-2 inhibition induced a two-fold larger decrease in SCC in UC patients. Despite being in clinical and endoscopic remission, quiescent UC patients demonstrated abnormal mucosal barrier properties at the molecular and functional level. Further exploration of mucosal molecular signature for revision of current remission standards should be considered.

Expression of tricellular tight junction proteins and the paracellular macromolecule barrier are recovered in remission of ulcerative colitis

“…As the main important finding of the present study tricellulin expression was found to be recovered towards normal in patients in complete remission. A similar tendency was also observed for tricellulin but still with a diminished claudin-4 expression when active and less active UC patients were analyzed [ 32 ]. In contrast to this study, our present analysis incorporated only patients without any inflammatory activity (with a normal Mayo endoscopic subscore), which enables us to conclude on a lack of any tricellulin impairment in complete remission.…”

Anti-ulcerative colitis effects of chemically characterized extracts from Calliandra haematocephala in acetic acid-induced ulcerative colitis

“…It regulates the production of proinflammatory cytokines and apoptotic mediators via the production of PGE2 and even is involved in malignant complications of UC. Its level in the inflamed colon is increased as was observed in the present study (Kjaergaard et al, 2020). CHME and CHnHE normalized the COX-2 level exhibiting the antiinflammatory potential that may be attributed to polyphenols detected in both extracts as also observed in another study (Abdallah et al, 2020).…”

Thiopurines: Recent Topics and Their Role in the Treatment of Inflammatory Bowel Diseases

“…Furthermore, thiopurine withdrawal needs to be justified based on assessment of remission with new imaging-enhanced endoscopy or molecular biological examination of tissue samples. Kjaergaard et al used mucosal biopsy specimens from patients with quiescent UC to analyze mucosal healing in quiescent UC at the molecular and functional level, and reported upregulations of tight junction proteins claudin-2 and claudin-4 mRNA levels, and downregulation of cyclooxygenase-1 enzyme mRNA levels (Kjaergaard et al, 2020). The use of tissue samples to explore mucosal molecular signatures may aid the assessment of remission and could potentially help in deciding when to temporarily withhold thiopurine treatment.…”