Trefoil factor family-peptides promote migration of human bronchial epithelial cells -: Synergistic effect with epidermal growth factor

Trefoil factor family-peptides promote migration of human bronchial epithelial cells -: Synergistic effect with epidermal growth factor
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DOI:
10.1165/ajrcmb.25.4.4429
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发表时间:
2001-10-01
影响因子:
6.4
通讯作者:
Hoffmann, W
Hoffmann, W
中科院分区:
医学1区
文献类型:
--
作者:
Oertel, M;Graness, A;Hoffmann, W

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一个被称为“恢复”的过程能够通过相邻细胞的迁移快速修复呼吸道上皮。粘蛋白相关的TFF-肽(以前称为P-结构域肽或三叶因子)是在模拟肠恢复的各种体外模型中增强细胞迁移的典型原动力。使用人支气管上皮细胞系BEAS-2B作为气道重建的模型系统。通过BEAS-2B细胞的体外伤口愈合测定证明重组人TFF 2以及猪TFF 2的运动原活性。TFF 2不诱导表皮生长因子(EGF)受体的磷酸化。EGF能够在3 × 10 - 10(-10)M的浓度下增强人TFF 2的运动原效应,而EGF本身(即,在不存在TFF 2的情况下)在该低浓度下不刺激迁移。此外,TFF 2以及TFF 3的单体和二聚体形式增强BEAS-2B细胞在Boyden室中的迁移。在Boyden室中,TFF 2对正常人支气管上皮(NHBE)细胞也显示出运动原活性。这些结果表明,TFF-肽在人呼吸道上皮细胞中起促动剂的作用,在气道疾病如哮喘的过程中触发受损粘膜的快速修复。
A process termed "restitution" enables rapid repair of the respiratory epithelium by migration of neighbouring cells. Mucin-associated TFF-pepticles (formerly P-domain peptides or trefoil factors) are typical motogens enhancing migration of cells in various in vitro models mimicking restitution of the intestine. The human bronchial epithelial cell line BEAS-2B was used as a model system of airway restitution. The motogenic activities of recombinant human TFF2 as well as porcine TFF2 were demonstrated by in vitro wound healing assays of BEAS-2B cells. TFF2 did not induce phosphorylation of the epidermal growth factor (EGF) receptor. EGF was capable of enhancing the motogenic effect of human TFF2 at a concentration of 3 X 10(-10) M whereas EGF itself (i.e., in the absence of TFF2) did not stimulate migration at this low concentration. Furthermore, TFF2 as well as monomeric and dimeric forms of TFF3 enhanced migration of BEAS-2B cells in Boyden chambers. Motogenic activity of TFF2 was also shown for normal human bronchial epithelial (NHBE) cells in Boyden chambers. These results suggest that TFF-pepticles act as motogens in the human respiratory epithelium triggering rapid repair of damaged mucosa in the course of airway diseases such as asthma.