Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis

Majken Lindholm*, Tina Manon-Jensen, Gunvor Iben Madsen, Aleksander Krag, Morten Asser Karsdal, Jens Kjeldsen, Joachim Høg Mortensen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background: Chronic intestinal inflammation results in tissue damage partly caused by an increase in matrix metalloproteinases (MMP) activity causing degradation of extracellular matrix (ECM) proteins. We studied intestinal tissue remodeling by quantifying ECM protein fragments in serum in dextran sulfate sodium (DSS)-induced colitis, to investigate ECM protein fragments as serological biomarkers of intestinal tissue remodeling and disease activity. Methods: Male Sprague–Dawley rats received 5% DSS in drinking water for 5 days followed by 11 days with regular water. Disease activity index (DAI) was scored daily. Serum was collected on day 0, 6, 7, and 16. ELISAs were used to quantify MMP-derived remodeling fragments of basement membrane type IV collagen (C4M and PRO-C4) and interstitial matrix type III collagen (C3M and rPRO-C3). Results: In DSS rats, serum levels relative to baseline of C4M, PRO-C4, and C3M were elevated (P < 0.01; P < 0.001; P < 0.001) at day 7, which declined at day 16. Levels of rPRO-C3 were lower in DSS rats at day 7 and increased to normal levels at day 16. The ratio between C3M and rPRO-C3 showed an overall degradation (P < 0.0001) of collagen type III in DSS rats at day 7, which correlated to the DAI (r 2 = 0.5588, P < 0.0001). Conclusion: Our data suggest that remodeling of the basement membrane (C4M and PRO-C4) and the interstitial matrix (C3M and rPRO-C3) increased during DSS-induced colitis and declined with reversal of the disease. Thus, serological biochemical biomarkers of the ECM reflect tissue remodeling and could be studied as markers of disease activity in IBD.

Original languageEnglish
JournalDigestive Diseases and Sciences
Volume64
Issue number11
Pages (from-to)3134-3142
ISSN0163-2116
DOIs
Publication statusPublished - Nov 2019

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Dextran Sulfate
Colitis
Extracellular Matrix Proteins
Collagen Type III
Matrix Metalloproteinases
Serum
Collagen Type IV

Keywords

  • Collagens
  • DSS-induced colitis
  • Extracellular matrix remodeling
  • Inflammatory bowel disease
  • Serological biomarkers

Cite this

@article{ae7a220091174308aa979293c41cb38c,
title = "Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis",
abstract = "Background: Chronic intestinal inflammation results in tissue damage partly caused by an increase in matrix metalloproteinases (MMP) activity causing degradation of extracellular matrix (ECM) proteins. We studied intestinal tissue remodeling by quantifying ECM protein fragments in serum in dextran sulfate sodium (DSS)-induced colitis, to investigate ECM protein fragments as serological biomarkers of intestinal tissue remodeling and disease activity. Methods: Male Sprague–Dawley rats received 5{\%} DSS in drinking water for 5 days followed by 11 days with regular water. Disease activity index (DAI) was scored daily. Serum was collected on day 0, 6, 7, and 16. ELISAs were used to quantify MMP-derived remodeling fragments of basement membrane type IV collagen (C4M and PRO-C4) and interstitial matrix type III collagen (C3M and rPRO-C3). Results: In DSS rats, serum levels relative to baseline of C4M, PRO-C4, and C3M were elevated (P < 0.01; P < 0.001; P < 0.001) at day 7, which declined at day 16. Levels of rPRO-C3 were lower in DSS rats at day 7 and increased to normal levels at day 16. The ratio between C3M and rPRO-C3 showed an overall degradation (P < 0.0001) of collagen type III in DSS rats at day 7, which correlated to the DAI (r 2 = 0.5588, P < 0.0001). Conclusion: Our data suggest that remodeling of the basement membrane (C4M and PRO-C4) and the interstitial matrix (C3M and rPRO-C3) increased during DSS-induced colitis and declined with reversal of the disease. Thus, serological biochemical biomarkers of the ECM reflect tissue remodeling and could be studied as markers of disease activity in IBD.",
keywords = "Collagens, DSS-induced colitis, Extracellular matrix remodeling, Inflammatory bowel disease, Serological biomarkers",
author = "Majken Lindholm and Tina Manon-Jensen and Madsen, {Gunvor Iben} and Aleksander Krag and Karsdal, {Morten Asser} and Jens Kjeldsen and Mortensen, {Joachim H{\o}g}",
year = "2019",
month = "11",
doi = "10.1007/s10620-019-05676-6",
language = "English",
volume = "64",
pages = "3134--3142",
journal = "Digestive Diseases and Sciences",
issn = "0163-2116",
publisher = "Springer",
number = "11",

}

Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis. / Lindholm, Majken; Manon-Jensen, Tina; Madsen, Gunvor Iben; Krag, Aleksander; Karsdal, Morten Asser; Kjeldsen, Jens; Mortensen, Joachim Høg.

In: Digestive Diseases and Sciences, Vol. 64, No. 11, 11.2019, p. 3134-3142.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Extracellular Matrix Fragments of the Basement Membrane and the Interstitial Matrix Are Serological Markers of Intestinal Tissue Remodeling and Disease Activity in Dextran Sulfate Sodium Colitis

AU - Lindholm, Majken

AU - Manon-Jensen, Tina

AU - Madsen, Gunvor Iben

AU - Krag, Aleksander

AU - Karsdal, Morten Asser

AU - Kjeldsen, Jens

AU - Mortensen, Joachim Høg

PY - 2019/11

Y1 - 2019/11

N2 - Background: Chronic intestinal inflammation results in tissue damage partly caused by an increase in matrix metalloproteinases (MMP) activity causing degradation of extracellular matrix (ECM) proteins. We studied intestinal tissue remodeling by quantifying ECM protein fragments in serum in dextran sulfate sodium (DSS)-induced colitis, to investigate ECM protein fragments as serological biomarkers of intestinal tissue remodeling and disease activity. Methods: Male Sprague–Dawley rats received 5% DSS in drinking water for 5 days followed by 11 days with regular water. Disease activity index (DAI) was scored daily. Serum was collected on day 0, 6, 7, and 16. ELISAs were used to quantify MMP-derived remodeling fragments of basement membrane type IV collagen (C4M and PRO-C4) and interstitial matrix type III collagen (C3M and rPRO-C3). Results: In DSS rats, serum levels relative to baseline of C4M, PRO-C4, and C3M were elevated (P < 0.01; P < 0.001; P < 0.001) at day 7, which declined at day 16. Levels of rPRO-C3 were lower in DSS rats at day 7 and increased to normal levels at day 16. The ratio between C3M and rPRO-C3 showed an overall degradation (P < 0.0001) of collagen type III in DSS rats at day 7, which correlated to the DAI (r 2 = 0.5588, P < 0.0001). Conclusion: Our data suggest that remodeling of the basement membrane (C4M and PRO-C4) and the interstitial matrix (C3M and rPRO-C3) increased during DSS-induced colitis and declined with reversal of the disease. Thus, serological biochemical biomarkers of the ECM reflect tissue remodeling and could be studied as markers of disease activity in IBD.

AB - Background: Chronic intestinal inflammation results in tissue damage partly caused by an increase in matrix metalloproteinases (MMP) activity causing degradation of extracellular matrix (ECM) proteins. We studied intestinal tissue remodeling by quantifying ECM protein fragments in serum in dextran sulfate sodium (DSS)-induced colitis, to investigate ECM protein fragments as serological biomarkers of intestinal tissue remodeling and disease activity. Methods: Male Sprague–Dawley rats received 5% DSS in drinking water for 5 days followed by 11 days with regular water. Disease activity index (DAI) was scored daily. Serum was collected on day 0, 6, 7, and 16. ELISAs were used to quantify MMP-derived remodeling fragments of basement membrane type IV collagen (C4M and PRO-C4) and interstitial matrix type III collagen (C3M and rPRO-C3). Results: In DSS rats, serum levels relative to baseline of C4M, PRO-C4, and C3M were elevated (P < 0.01; P < 0.001; P < 0.001) at day 7, which declined at day 16. Levels of rPRO-C3 were lower in DSS rats at day 7 and increased to normal levels at day 16. The ratio between C3M and rPRO-C3 showed an overall degradation (P < 0.0001) of collagen type III in DSS rats at day 7, which correlated to the DAI (r 2 = 0.5588, P < 0.0001). Conclusion: Our data suggest that remodeling of the basement membrane (C4M and PRO-C4) and the interstitial matrix (C3M and rPRO-C3) increased during DSS-induced colitis and declined with reversal of the disease. Thus, serological biochemical biomarkers of the ECM reflect tissue remodeling and could be studied as markers of disease activity in IBD.

KW - Collagens

KW - DSS-induced colitis

KW - Extracellular matrix remodeling

KW - Inflammatory bowel disease

KW - Serological biomarkers

U2 - 10.1007/s10620-019-05676-6

DO - 10.1007/s10620-019-05676-6

M3 - Journal article

VL - 64

SP - 3134

EP - 3142

JO - Digestive Diseases and Sciences

JF - Digestive Diseases and Sciences

SN - 0163-2116

IS - 11

ER -