Abstract
Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's disease (CD). The contribution of epithelial to mesenchymal transition (EMT) to the mesenchymal cell pool in CD fibrosis remains obscure. The miR‐200 family regulates fibrosis‐related EMT in organs other than the gut. E‐cadherin, cytokeratin‐18 and vimentin expression was assessed using immunohistochemistry on paired strictured (SCD) and non‐strictured (NSCD) ileal CD resections and correlated with fibrosis grade. MiR‐200 expression was measured in paired SCD and NSCD tissue compartments using laser capture microdissection and RT‐qPCR. Serum miR‐200 expression was also measured in healthy controls and CD patients with stricturing and non‐stricturing phenotypes. Extra‐epithelial cytokeratin‐18 staining and vimentin‐positive epithelial staining were significantly greater in SCD samples (P = 0.04 and P = 0.03, respectively). Cytokeratin‐18 staining correlated positively with subserosal fibrosis (P < 0.001). Four miR‐200 family members were down‐regulated in fresh SCD samples (miR‐141, P = 0.002; miR‐200a, P = 0.002; miR‐200c, P = 0.001; miR‐429; P = 0.004); miR‐200 down‐regulation in SCD tissue was localised to the epithelium (P = 0.001‐0.015). The miR‐200 target ZEB1 was up‐regulated in SCD samples (P = 0.035). No difference in serum expression between patient groups was observed. Together, these observations suggest the presence of EMT in CD strictures and implicate the miR‐200 family as regulators. Functional studies to prove this relationship are now warranted.
Highlights
Crohn's disease (CD) is a chronic, inflammatory, relapsing and remitting condition that predominantly affects the gastrointestinal tract.Research focussed on intestinal barrier function, host immune responses, genetic susceptibility and the gut microbiota has advanced our understanding of the aetiopathogenesis of inflammatory CD
In conjunction with IHC evidence of epithelial to mesenchymal transition (EMT) occurring in association with fibrosis in intestinal resection specimens from patients with CD, we sought to measure expression of the miR‐200 family in eight paired NSCD and SCD samples of whole tissue
Published data suggest a contribution of EMT to the development of intestinal fibrosis in mouse models,[30] there are only very few reports of cellular EMT events in human CD.[31,32,37]
Summary
Crohn's disease (CD) is a chronic, inflammatory, relapsing and remitting condition that predominantly affects the gastrointestinal tract. Two recent studies of type 2 EMT have provided evidence for the concept of “partial EMT”27,28 whereby cells lose epithelial characteristics but promote fibrosis by means other than the active deposition of extracellular matrix within the deeper tissue layers. These include the secretion of exosomes and cytokines to promote the differentiation of fibroblasts to myofibroblasts and the recruitment of bone‐marrow derived mesenchymal cells. We assessed serum levels of the miR‐200 family in different CD phenotypes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
