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A Serological Biomarker of Laminin Gamma 1 Chain Degradation Reflects Altered Basement Membrane Remodeling in Crohn’s Disease and DSS Colitis

Lindholm, M; Di Sabatino, A; Manon-Jensen, T; Mazza, G; Madsen, G; Giuffrida, P; Pinzani, M; ... Mortensen, JH; + view all (2022) A Serological Biomarker of Laminin Gamma 1 Chain Degradation Reflects Altered Basement Membrane Remodeling in Crohn’s Disease and DSS Colitis. Digestive Diseases and Sciences , 67 pp. 3662-3671. 10.1007/s10620-021-07252-3. Green open access

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Abstract

Background: The laminin gamma 1 chain (LMγ1) is abundant along the crypt-villus axis in the intestinal basement membrane. / Aims: We investigated whether a serological biomarker of laminin degradation was associated with disease activity in patients with Crohn’s disease (CD) and in rats with dextran sulfate sodium (DSS)-induced colitis. / Methods: Serum samples from CD patients (n = 43), healthy subjects (n = 19), and Sprague Dawley rats receiving 5–6% DSS water for five days and regular drinking water for 11 days were included in this study. The LG1M biomarker, a neo-epitope degradation fragment of the LMγ1 chain generated by matrix metalloproteinases-9 (MMP-9), was measured in serum to estimate the level of laminin degradation. / Results: Serum LG1M was elevated in CD patients with active and inactive disease compared to healthy subjects (p < 0.0001). LG1M distinguished CD patients from healthy subjects, with an area under the curve (AUC) of 0.81 (p < 0.0001). Serum LG1M was decreased in DSS rats compared to controls 2 days after DSS withdrawal, and increased upon reversal of the disease. / Conclusions: Increased serum LG1M in active and inactive CD patients supports the evidence of altered LM expression in both inflamed and non-inflamed tissue. Moreover, lower LG1M levels in the early healing phase of DSS-induced colitis may reflect ongoing mucosal repair.

Type: Article
Title: A Serological Biomarker of Laminin Gamma 1 Chain Degradation Reflects Altered Basement Membrane Remodeling in Crohn’s Disease and DSS Colitis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10620-021-07252-3
Publisher version: https://doi.org/10.1007/s10620-021-07252-3
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Inflammatory bowel disease, Laminin, Biomarkers, Crohn's disease, DSS colitis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10142273
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