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Inflamm Bowel Dis. 2011 Aug;17(8):1665-73. doi: 10.1002/ibd.21543. Epub 2011 Feb 1.

N-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.

Author information

1
Department of Surgery, St. Vincent's University Hospital, Dublin, Ireland.

Abstract

BACKGROUND:

Intestinal fibroblasts mediate stricture formation in Crohn's disease (CD). Transforming growth factor-β₁ (TGF-β₁) is important in fibroblast activation, while cell attachment and migration is regulated by the adhesion molecule N-cadherin. The aim of this study was to investigate the expression and function of N-cadherin in intestinal fibroblasts in patients with fibrostenosing CD.

METHODS:

Intestinal fibroblasts were cultured from seromuscular biopsies from patients undergoing resection for terminal ileal fibrostenosing CD (n = 14) or controls patients (n = 8). N-cadherin expression was assessed using Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fibroblasts were stimulated with TGF-β₁ and selective pathway inhibitors Y27632, PD98050, and LY294002 were used to examine the Rho/ROCK, ERK-1/2, and Akt signaling pathways, respectively. Cell migration was assessed using a scratch wound assay. N-cadherin was selectively overexpressed using a plasmid.

RESULTS:

Fibroblasts from fibrostenosing CD express increased constitutive N-cadherin mRNA and protein and exhibit enhanced basal cell migration relative to those from directly adjacent normal bowel. Control fibroblasts treated with TGF-β₁ induced N-cadherin in a dose-dependent manner which was inhibited by Rho/ROCK and Akt pathway modulation. Control fibroblasts exhibited enhanced cell migration in response to treatment with TGF-β₁ or transfection with an N-cadherin plasmid.

CONCLUSIONS:

Fibroblasts from strictures in CD express increased constitutive N-cadherin and exhibit enhanced basal cell migration. TGF-β₁ is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-β₁-mediated induction of N-cadherin may potentiate Crohn's stricture formation.

PMID:
21287659
DOI:
10.1002/ibd.21543
[Indexed for MEDLINE]

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