Insulin-like growth factor binding proteins 3 and 5 are overexpressed in idiopathic pulmonary fibrosis and contribute to extracellular matrix deposition
Insulin-like growth factor binding proteins 3 and 5 are overexpressed in idiopathic pulmonary fibrosis and contribute to extracellular matrix deposition
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DOI：
10.1016/s0002-9440(10)62263-8
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发表时间：
2005-02-01
影响因子：
6
通讯作者：
Feghali-Bostwick, CA
中科院分区：
文献类型：
--
作者：
Pilewski, JM;Liu, LX;Feghali-Bostwick, CA
特发性肺纤维化（IPF）是一种病因不明的纤维化疾病，可导致显著的发病率和死亡率。IPF的发病机制尚不完全清楚。由于最近的研究表明胰岛素样生长因子-I（IGF-I）参与了纤维化的发病机制，我们研究了胰岛素样生长因子结合蛋白（IGFBP）-3和-5在IPF中的表达和功能。在IPF肺组织中，IGFBP-3和-5水平在体内增加，在IPF肺培养的成纤维细胞中，IGFBP-3和-5水平在体外增加。由IPF成纤维细胞分泌的IGFBPs具有功能活性并且可以结合IGF-I，并且由原代成纤维细胞分泌的IGFBPs结合细胞外基质组分。我们的研究结果还表明，IGFBPs可能参与启动和/或永久的纤维化，凭借他们的能力，诱导生产的细胞外基质成分，如胶原蛋白I型和纤连蛋白在正常的初级成人肺成纤维细胞。虽然转化生长因子-β以时间依赖性方式增加原代成纤维细胞的IGFBP-3产生，但转化生长因子-β并不增加IGFBP-5水平。总之，我们的结果表明IGFBPs在IPF纤维化的发展中起重要作用。
Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown etiology that results in significant morbidity and mortality. The pathogenesis of IPF is not completely understood. Because recent studies have implicated insulin-like growth factor-I (IGF-I) in the pathogenesis of fibrosis, we examined the expression and function of insulin-like growth factor binding proteins (IGFBP)-3 and -5 in IPF. IGFBP-3 and -5 levels were increased in vivo in IPF lung tissues and in vitro in fibroblasts cultured from IPF lung. The IGFBPs secreted by IPF fibroblasts are functionally active and can bind IGF-I, and IGFBPs secreted by primary fibroblasts bind extracellular matrix components. Our results also suggest that IGFBPs may be involved in the initiation and/or perpetuation of fibrosis by virtue of their ability to induce the production of extracellular matrix components such as collagen type I and fibronectin in normal primary adult lung fibroblasts. Although transforming growth factor-beta increased IGFBP-3 production by primary fibroblasts in a time-dependent manner, IGFBP-5 levels were not increased by transforming growth factor-beta. Taken together, our results suggest that IGFBPs play an important role in the development of fibrosis in IPF.