Beddy D, Watson R W G, Fitzpatrick J M, O'Connell P R
Department of Surgery, Mater Misericordiae Hospital and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Br J Surg. 2004 Jan;91(1):72-7. doi: 10.1002/bjs.4453.
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.
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.
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.
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.
血管内皮生长因子（VEGF）是一种强效血管生成因子，与早期伤口愈合和纤维化有关。成纤维细胞可能通过VEGF的过度表达引发克罗恩病的狭窄形成。本研究的目的是检测从克罗恩病患者分离的成纤维细胞中VEGF的表达及调控情况。
采用原代外植体技术，从8例因克罗恩病接受肠切除手术患者的无狭窄和狭窄肠段的浆膜活检组织中分离成纤维细胞，并从6例因结直肠癌接受切除手术患者的正常结肠组织中分离成纤维细胞。将成纤维细胞与转化生长因子（TGF）β和皮质类固醇一起培养。24小时后收集培养上清液，通过酶联免疫吸附测定法检测VEGF。
在克罗恩病患者中，从狭窄部位分离的成纤维细胞（均值（标准误）1980（260）pg/ml）产生的VEGF显著高于无狭窄肠段（1116（165）pg/ml）或对照成纤维细胞（898（93）pg/ml）。TGF-β增加正常和无狭窄克罗恩病成纤维细胞的VEGF产生。皮质类固醇抑制所有组中未受刺激的VEGF产生。
浆膜成纤维细胞VEGF产生增加可能在克罗恩病狭窄形成起始中起作用。浆膜成纤维细胞中VEGF的产生对TGF-β刺激敏感。皮质类固醇可能通过抑制VEGF减少狭窄形成。
