No Longer Stretching Credibility: Mechanical Force Meets Inflammation in Experimental Intestinal Stenosis

Excerpt

The pathophysiology of Crohn’s disease (CD) is rooted in a complex interplay of genetic, immunological, and environmental factors [1]. The heterogeneity of the underlying mechanisms of disease is mirrored by the heterogeneous disease manifestations in different segments of the GI tract. Though intestinal fibrosis leading to stenosis is recognized as a major complication of CD, its mechanisms remain largely elusive [1]. Current concepts of its pathogenesis suggest that intestinal stenosis requires initiation through an inflammatory insult leading to tissue damage, fibrosis, and ultimately stenosis in patients with CD [1]. It has however become apparent that once established, fibrosis can evolve independently of inflammation, as has been shown for extraintestinal fibrosis, as well as for intestinal fibrogenesis [1‐3]. One putative mechanism driving the inflammation-independent progression of fibrosis is the mechanical properties of a given intestinal tissue [3]. The stiffness of the intestine in inflammation is increased compared with unaffected segments [4]; the stiffness of strictured segments is approximately six times higher compared with non-strictured segments. [3] Stiffness of the extracellular matrix (ECM) environment itself is a driver of mesenchymal cell activation to produce more ECM in a forward-feeding loop eventuating in intestinal obstruction. …