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

Hdl Handle:
http://hdl.handle.net/10147/207511
Title:
N-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.
Authors:
Burke, John P; Cunningham, Michael F; Sweeney, Catherine; Docherty, Neil G; O'Connell, P Ronan
Affiliation:
Department of Surgery, St. Vincent's University Hospital, Dublin, Ireland.
Citation:
Inflamm Bowel Dis. 2011 Aug;17(8):1665-73. doi: 10.1002/ibd.21543. Epub 2011 Feb , 1.
Journal:
Inflammatory bowel diseases
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207511
DOI:
10.1002/ibd.21543
PubMed ID:
21287659
Abstract:
BACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn's disease (CD). Transforming growth factor-beta (TGF-beta) 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-beta 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-beta 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-beta 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-beta is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-beta-mediated induction of N-cadherin may potentiate Crohn's stricture formation.
Language:
eng
MeSH:
Adult; Analysis of Variance; Cadherins/genetics/*metabolism/physiology; Cell Movement/physiology; Cells, Cultured; Constriction, Pathologic/metabolism/pathology; Crohn Disease/*metabolism/*pathology; Female; Fibroblasts/drug effects/*metabolism/physiology; Fibrosis; Humans; Ileum/*pathology; Male; RNA, Messenger/*metabolism; Signal Transduction/physiology; Transforming Growth Factor beta1/pharmacology; Up-Regulation/genetics
ISSN:
1536-4844 (Electronic); 1078-0998 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorBurke, John Pen_GB
dc.contributor.authorCunningham, Michael Fen_GB
dc.contributor.authorSweeney, Catherineen_GB
dc.contributor.authorDocherty, Neil Gen_GB
dc.contributor.authorO'Connell, P Ronanen_GB
dc.date.accessioned2012-02-01T10:29:54Z-
dc.date.available2012-02-01T10:29:54Z-
dc.date.issued2012-02-01T10:29:54Z-
dc.identifier.citationInflamm Bowel Dis. 2011 Aug;17(8):1665-73. doi: 10.1002/ibd.21543. Epub 2011 Feb , 1.en_GB
dc.identifier.issn1536-4844 (Electronic)en_GB
dc.identifier.issn1078-0998 (Linking)en_GB
dc.identifier.pmid21287659en_GB
dc.identifier.doi10.1002/ibd.21543en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207511-
dc.description.abstractBACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn's disease (CD). Transforming growth factor-beta (TGF-beta) 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-beta 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-beta 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-beta 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-beta is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-beta-mediated induction of N-cadherin may potentiate Crohn's stricture formation.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAnalysis of Varianceen_GB
dc.subject.meshCadherins/genetics/*metabolism/physiologyen_GB
dc.subject.meshCell Movement/physiologyen_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshConstriction, Pathologic/metabolism/pathologyen_GB
dc.subject.meshCrohn Disease/*metabolism/*pathologyen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFibroblasts/drug effects/*metabolism/physiologyen_GB
dc.subject.meshFibrosisen_GB
dc.subject.meshHumansen_GB
dc.subject.meshIleum/*pathologyen_GB
dc.subject.meshMaleen_GB
dc.subject.meshRNA, Messenger/*metabolismen_GB
dc.subject.meshSignal Transduction/physiologyen_GB
dc.subject.meshTransforming Growth Factor beta1/pharmacologyen_GB
dc.subject.meshUp-Regulation/geneticsen_GB
dc.titleN-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.en_GB
dc.contributor.departmentDepartment of Surgery, St. Vincent's University Hospital, Dublin, Ireland.en_GB
dc.identifier.journalInflammatory bowel diseasesen_GB
dc.description.provinceLeinster-

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