Interstitial fibrosis and growth factors.
Interstitial fibrosis and growth factors.
复制标题
DOI：
10.1289/ehp.00108s4751
复制
发表时间：
2000-08
影响因子：
10.4
通讯作者：
Brody AR
中科院分区：
文献类型：
--
作者：
Lasky JA;Brody AR
间质性肺纤维化（IPF）是由多种吸入剂（包括矿物颗粒、有机粉尘和氧化剂气体）引起的肺部疤痕。这种疾病困扰着全世界数百万人，目前还没有有效的治疗方法。缺乏有效治疗的一个主要原因是，很少有疾病的分子机制被充分定义，以设计适当的治疗靶点。我们的实验室专注于分子机制，通过这些机制，三种选定的肽生长因子可以在IPF的发展中发挥作用。数百种生长因子和细胞因子可能参与复杂的疾病过程。我们正在研究血小板源性生长因子，因为它是迄今为止描述的最有效的间充质细胞有丝分裂原，转化生长因子β，因为它是间充质细胞的细胞外基质（瘢痕组织）组分的强大诱导剂，肿瘤坏死因子α，因为它是一种多效性细胞因子，我们和其他人已经证明在动物模型中对IPF的发展至关重要。本文综述了一些证据，从研究中，在人类，动物模型，并在体外，支持生长因子假说。使用现代分子和转基因技术可以阐明这些目标，将允许有效的治疗方法。
Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety of inhaled agents including mineral particles, organic dusts, and oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for therapy. Our laboratory has focused on the molecular mechanisms through which three selected peptide growth factors could play a role in the development of IPF. Hundreds of growth factors and cytokines could be involved in the complex disease process. We are studying platelet-derived growth factor because it is the most potent mesenchymal cell mitogen yet described, transforming growth factor beta because it is a powerful inducer of extracellular matrix (scar tissue) components by mesenchymal cells, and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches.