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

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Kjærgaard, Sebastian ; Damm, Morten M B ; Chang, Joan ; Riis, Lene B ; Rasmussen, Hanne B ; Hytting-Andreasen, Rasmus ; Krug, Susanne M ; Schulzke, Jörg-Dieter ; Bindslev, Niels ; Hansen, Mark Berner. / Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis : Are These Potential Normalization Criteria?. I: International Journal of Molecular Sciences. 2020 ; Bind 21, Nr. 5.

Bibtex

@article{ed8b79af90174b30b21de307f7ec47a1,
title = "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.",
keywords = "Adult, Aged, Biopsy, Case-Control Studies, Claudin-1/genetics, Claudins/genetics, Colitis, Ulcerative/genetics, Cyclooxygenase 1/genetics, Cyclooxygenase 2/genetics, Female, Gene Expression Regulation, Gene Regulatory Networks, Humans, MARVEL Domain Containing 2 Protein/genetics, Male, Middle Aged, Young Adult",
author = "Sebastian Kj{\ae}rgaard and Damm, {Morten M B} and Joan Chang and Riis, {Lene B} and Rasmussen, {Hanne B} and Rasmus Hytting-Andreasen and Krug, {Susanne M} and J{\"o}rg-Dieter Schulzke and Niels Bindslev and Hansen, {Mark Berner}",
year = "2020",
month = mar,
day = "10",
doi = "10.3390/ijms21051887",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Molecular Diversity Preservation International (M D P I)",
number = "5",

}

RIS

TY - JOUR

T1 - Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis

T2 - Are These Potential Normalization Criteria?

AU - Kjærgaard, Sebastian

AU - Damm, Morten M B

AU - Chang, Joan

AU - Riis, Lene B

AU - Rasmussen, Hanne B

AU - Hytting-Andreasen, Rasmus

AU - Krug, Susanne M

AU - Schulzke, Jörg-Dieter

AU - Bindslev, Niels

AU - Hansen, Mark Berner

PY - 2020/3/10

Y1 - 2020/3/10

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Biopsy

KW - Case-Control Studies

KW - Claudin-1/genetics

KW - Claudins/genetics

KW - Colitis, Ulcerative/genetics

KW - Cyclooxygenase 1/genetics

KW - Cyclooxygenase 2/genetics

KW - Female

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Humans

KW - MARVEL Domain Containing 2 Protein/genetics

KW - Male

KW - Middle Aged

KW - Young Adult

U2 - 10.3390/ijms21051887

DO - 10.3390/ijms21051887

M3 - Journal article

C2 - 32164249

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 5

ER -

ID: 62408280