Differential Expression of Soluble Receptor for Advanced Glycation End-products in Mice Susceptible or Resistant to Chronic Colitis

Michael Bramhall, Kevin Rich, Ajanta Chakraborty, Larisa Logunova, Namshik Han, James Wilson, John McLaughlin, Andy Brass, Sheena M. Cruickshank

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

BACKGROUND: Identifying the factors that contribute to chronicity in inflamed colitic tissue is not trivial. However, in mouse models of colitis, we can investigate at preclinical timepoints. We sought to validate murine Trichuris muris infection as a model for identification of factors that promote development of chronic colitis. METHODS: We compared preclinical changes in mice with a resolving immune response to T. muris (resistant) vs mice that fail to expel the worms and develop chronic colitis (susceptible). Findings were then validated in healthy controls and patients with suspected or confirmed IBD. RESULTS: The receptor for advanced glycation end products (RAGE) was highly dysregulated between resistant and susceptible mice before the onset of any pathological signs. Increased soluble RAGE (sRAGE) in the serum and feces of resistant mice correlated with reduced colitis scores. Mouse model findings were validated in a preliminary clinical study: fecal sRAGE was differentially expressed in patients with active IBD compared with IBD in remission, patients with IBD excluded, or healthy controls. CONCLUSIONS: Preclinical changes in mouse models can identify early pathways in the development of chronic inflammation that human studies cannot. We identified the decoy receptor sRAGE as a potential mechanism for protection against chronic inflammation in colitis in mice and humans. We propose that the RAGE pathway is clinically relevant in the onset of chronic colitis and that further study of sRAGE in IBD may provide a novel diagnostic and therapeutic target.

Original languageEnglish
Pages (from-to)360-368
Number of pages9
JournalInflammatory Bowel Diseases
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 2020

Keywords

  • colitis
  • mouse
  • sRAGE

Cite this

Bramhall, M., Rich, K., Chakraborty, A., Logunova, L., Han, N., Wilson, J., McLaughlin, J., Brass, A., & Cruickshank, S. M. (2020). Differential Expression of Soluble Receptor for Advanced Glycation End-products in Mice Susceptible or Resistant to Chronic Colitis. Inflammatory Bowel Diseases, 26(3), 360-368. https://doi.org/10.1093/ibd/izz311