Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn's disease.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that is implicated in early wound healing and fibrosis. Fibroblasts may initiate stricture formation in Crohn's disease through overexpression of VEGF. The aim of this study was to examine VEGF expression and regulation in fibroblasts isolated from patients with Crohn's disease.


METHODS
Fibroblasts were isolated by a primary explant technique from serosal biopsies of non-strictured and strictured segments of bowel from eight patients undergoing resection for Crohn's disease, and normal colon from six patients undergoing resection for benign and malignant colorectal disease. Fibroblasts were cultured with transforming growth factor (TGF) beta and corticosteroids. After 24 h the culture supernatant was collected for VEGF assay by enzyme-linked immunosorbent assay.


RESULTS
VEGF production was significantly higher in fibroblasts isolated from strictures (mean(s.e.m.) 1980(260) pg/ml) than from non-strictured segments (1116(165) pg/ml) in patients with Crohn's disease or control fibroblasts (898(93) pg/ml). TGF-beta increased VEGF production in normal and non-strictured Crohn's fibroblasts. Corticosteroids suppressed unstimulated VEGF production in all groups.


CONCLUSIONS
Enhanced serosal fibroblast VEGF production might play a role in initiating stricture formation in Crohn's disease. VEGF production in serosal fibroblasts is sensitive to stimulation with TGF-beta. Corticosteroids may reduce stricturing through suppression of VEGF.
Beddy
D
D
Department of Surgery, Mater Misericordiae Hospital and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Watson
R W G
RW
Fitzpatrick
J M
JM
O'Connell
P R
PR
D000328:Adult; D000704:Analysis of Variance; D003424:Crohn Disease / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A