The chronic inflammation of Crohn's disease frequently leads to fibrosis and muscular hypertrophy of the intestinal wall. This often culminates in strictures, a serious condition lacking directed therapy. Severe pathological changes occur in the submucosa and muscularis propria intestinal wall layers of strictures, yet stricture-associated proteome changes in these layers is unexplored. We perform unbiased proteomics on submucosa and muscularis propria microdissected from transmural sections of strictured and non-strictured ileum. Proteome changes in stricture submucosa reflect a transition from homeostasis to tissue remodeling, inflammation and smooth muscle alterations. Top submucosa features include reduced vascular components and lipid metabolism proteins accompanied by increased proteins with immune-, matrix- or stress functions including CTHRC1, TNC, IL16, MZB1 and TXNDC5. In parallel, predominant changes in stricture muscularis propria include increased matrix (POSTN) and immune (mast cell CPA3) proteins alongside decreased proteins with lipid metabolic, mitochondrial or key muscle functions. Finally, trends of differentially expressed proteins along non-stricture submucosa suggest progressive profibrotic tissue remodeling and muscle expansion as proximity to stricture increases. The comprehensive proteome map presented here offers unique layer-resolved insight into the stricture microenvironment and potential drivers of fibrotic disease, providing a valuable resource to fuel biomarker and therapeutic target research. Keywords: Crohn's disease strictures, proteomics, intestinal fibrosis, fibrostenosis.
Alfredsson et al. (Tue,) studied this question.
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