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

Majken Lindholm, Antonio Di Sabatino, Tina Manon-Jensen, Giuseppe Mazza, Gunvor I. Madsen, Paolo Giuffrida, Massimo Pinzani, Aleksander Krag, Morten A. Karsdal, Jens Kjeldsen, Joachim H. Mortensen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalDigestive Diseases and Sciences
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Biomarkers
  • Crohn’s disease
  • DSS colitis
  • Inflammatory bowel disease
  • Laminin

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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