Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair
Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair
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DOI：
10.1073/pnas.101130898
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发表时间：
2001-05-22
影响因子：
11.1
通讯作者：
Levi-Schaffer, F
中科院分区：
文献类型：
--
作者：
Micera, A;Vigneti, E;Levi-Schaffer, F
神经生长因子（NGF）是一种多肽，除了其对神经细胞的作用之外，据信其在炎症反应和组织修复中起作用。由于成纤维细胞代表了这些过程中的主要靶细胞和效应细胞，为了研究NGF是否参与肺和皮肤组织修复，我们研究了NGF对成纤维细胞迁移、增殖、胶原代谢、成肌成纤维细胞调制和胶原凝胶收缩的影响。皮肤和肺成纤维细胞被发现产生神经生长因子和表达酪氨酸激酶受体（trkA）的基础条件下，而低亲和力的p75受体的表达，只有在长时间的神经生长因子暴露。在Boyden室中，NGF在受伤的成纤维细胞和皮肤迁移的体外模型中显著诱导皮肤和肺成纤维细胞迁移。然而，神经生长因子没有影响皮肤或肺成纤维细胞增殖，胶原蛋白的产生，或金属蛋白酶的生产或激活。相反，培养肺和皮肤成纤维细胞与神经生长因子调制成肌成纤维细胞的表型。此外，添加神经生长因子的胶原凝胶包埋的两种类型的成纤维细胞增加了他们的收缩。纤维化的人肺或皮肤组织显示NGF、trkA和p75的免疫反应性。这些数据显示了NGF对皮肤和肺成纤维细胞的直接促纤维化作用，因此表明了NGF在组织修复和纤维化中的作用。
Nerve growth factor (NGF) is a polypeptide which, in addition to its effect on nerve cells, is believed to play a role in inflammatory responses and in tissue repair. Because fibroblasts represent the main target and effector cells in these processes, to investigate whether NGF is involved in lung and skin tissue repair, we studied the effect of NGF on fibroblast migration, proliferation, collagen metabolism, modulation into myofibroblasts, and contraction of collagen gel. Both skin and lung fibroblasts were found to produce NGF and to express tyrosine kinase receptor (trkA) under basal conditions, whereas the low-affinity p75 receptor was expressed only after prolonged NGF exposure. NGF significantly induced skin and lung fibroblast migration in an in vitro model of wounded fibroblast and skin migration in Boyden chambers. Nevertheless NGF did not influence either skin or lung fibroblast proliferation, collagen production, or metalloproteinase production or activation. In contrast, culture of both lung and skin fibroblasts with NGF modulated their phenotype into myofibroblasts. Moreover, addition of NGF to both fibroblast types embedded in collagen gel increased their contraction. Fibrotic human lung or skin tissues displayed immunoreactivity for NGF, trkA, and p75. These data show a direct pro-fibrogenic effect of NGF on skin and lung fibroblasts and therefore indicate a role for NGF in tissue repair and fibrosis.