FIBROBLAST GROWTH-FACTORS MODULATE INTESTINAL EPITHELIAL-CELL GROWTH AND MIGRATION

FIBROBLAST GROWTH-FACTORS MODULATE INTESTINAL EPITHELIAL-CELL GROWTH AND MIGRATION
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DOI:
10.1016/0016-5085(94)90017-5
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发表时间:
1994-05-01
期刊:
影响因子:
29.4
通讯作者:
PODOLSKY, DK
PODOLSKY, DK
中科院分区:
医学1区
文献类型:
--
作者:
DIGNASS, AU;TSUNEKAWA, S;PODOLSKY, DK

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背景/目的:已发现多种多肽生长因子在上皮细胞群中发挥功能作用。本研究评价了某些成纤维细胞生长因子(酸性成纤维细胞生长因子、碱性成纤维细胞生长因子和角质形成细胞生长因子)在肠上皮细胞增殖和修复中的作用。方法:将重组生长因子加入IEC-6、Caco-2和HT-29细胞系的融合培养中,并检测[~3H]-胸腺嘧啶核苷掺入。通过对IEC-6细胞融合单层中建立的标准创面中细胞迁移的数量来评估其对体外修复模型的影响。结果:酸性成纤维细胞生长因子、碱性成纤维细胞生长因子和角质形成细胞生长因子对IEC-6、CaCO-2和HT-29细胞的增殖有轻度的促进作用。酸性成纤维细胞生长因子和碱性成纤维细胞生长因子可促进肠上皮细胞在体外重建10倍以上,并增强转化生长因子-β信使核糖核酸和蛋白的表达。结论:作用于成纤维细胞的成纤维细胞生长因子对肠上皮细胞群也有影响,可能有助于促进肠上皮细胞的修复,这是转化生长因子-β依赖的肠道创面愈合的初始步骤。
Background/Aims:Various peptide growth factors have been found to exert functional effects among epithelial cell populations. This study assessed the role of certain fibroblast growth factors (FGFs) (acidic FGF, basic FGF, and keratinocyte growth factor) in the regulation of intestinal epithelial cell proliferation and restitution.Methods:Recombinant growth factors were added to subconfluent cultures of IEC-6, Caco-2, and HT-29 cell lines with subsequent assessment of [3H]-thymidine incorporation. The effects on an in vitro model of restitution were assessed by quantitation of cells migrating into standard wounds established in confluent monolayers of IEC-6 cells. Transforming growth factor β (TGF-β) content of growth factortreated wounded monolayers was assessed by Northern blot and bioassay.Results:Acidic FGF, basic FGF, and keratinocyte growth factor caused a modest increase in proliferation of IEC-6, Caco-2, and HT-29 cell lines. Acidic FGF and basic FGF promoted intestinal epithelial cell restitution in vitro up to 10-fold, in conjunction with the enhanced expression of TGF-β messenger RNA and protein. Promotion of IEC-6 restitution by acidic and basic FGF could be blocked by addition of immunoneutralizing anti-TGF-β antisera.Conclusions:FGFs that exert effects on fibroblast cells also exert effects on intestinal epithelial cell populations and may help promote epithelial cell restitution, the initial step of intestinal wound healing through a TGF-β-dependent pathway.