Distinct patterns of insulin-like growth factor binding protein (IGFBP)-2 and TGFBP-3 expression in oxidant exposed lung epithelial cells
Distinct patterns of insulin-like growth factor binding protein (IGFBP)-2 and TGFBP-3 expression in oxidant exposed lung epithelial cells
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DOI：
10.1016/s0167-4889(00)00136-1
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发表时间：
2001-02-05
影响因子：
5.1
通讯作者：
Clement, A
中科院分区：
文献类型：
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作者：
Besnard, V;Corroyer, S;Clement, A
氧气 (O-2) 与多种肺部疾病有关。在构成肺的各种细胞类型中，肺泡结构的上皮细胞似乎是氧化损伤的主要目标。尽管它们在修复过程中很重要，但调节肺泡上皮干细胞（2 型细胞）复制的机制仍然知之甚少。基于几项研究的结果，这些研究记录了胰岛素样生长因子（IGF）系统参与肺上皮细胞复制，并且还表明IGF结合蛋白（IGFBP）在控制细胞增殖中的作用，本工作的目的是确定IGFBP是否可以参与调节暴露于氧化剂的人肺上皮细胞的生长。使用人肺腺癌细胞系 (A549) 进行实验，该细胞系暴露于高氧 (95% O-2) 不同时间。我们观察到仅接触 O-2 24 小时后细胞就出现了快速且可逆的生长停滞。当氧化损伤延长时，生长停滞后会诱导细胞凋亡并激活 Fas 途径。这些作用与 IGFBP-2 和 IGFBP-3 表达增加有关。此外，对这些蛋白质定位的研究揭示了不同的分布模式。 IGFBP-3主要存在于细胞外室。相比之下，分泌的 IGFBP-2 部分较不丰富，而细胞内区室中的 IGFBP-2 部分则显得较强。此外，亚细胞定位分析提供的数据表明细胞核中存在 IGFBP-2。综合起来，这些数据支持 IGFBP-2 的作用。和 IGFBP-3 在暴露于氧化剂后肺上皮细胞生长停滞和凋亡过程中的作用。他们还表明，不同的机制可能将 IGFBP-2 和 IGFBP-3 与细胞周期的关键调节因子联系起来。 (C) 2001 Elsevier Science B.V. 保留所有权利。
Oxygen (O-2) species are involved in a large variety of pulmonary diseases. Among the various cell types that compose the lung, the epithelial cells of the alveolar structure appear to be a major target for oxidant injury. Despite their importance in the repair processes, the mechanisms which regulate the replication of the stem cells of the alveolar epithelium, the type 2 cells, remain poorly understood. Based on the results of several studies which have documented the involvement of the insulin-like growth factor (IGF) system in lung epithelial cell replication, and which have also suggested a role for IGF binding proteins (IGFBPs) in the control of cell proliferation, the aim of the present work was to determine whether IGFBPs could be involved in the modulation of growth of human lung epithelial cells exposed to oxidants. Experiments were performed using a human lung adenocarcinoma cell line (A549) which was exposed for various durations to hyperoxia (95% O-2). We observed a rapid and reversible growth arrest of the cells after only 24 h of O-2 exposure. When oxidant injury was prolonged, growth arrest was followed by induction of apoptosis with activation of the Fas pathway. These effects were associated with an increased expression of IGFBP-2 and IGFBP-3. In addition, study of localization of these proteins revealed distinct patterns of distribution. IGFBP-3 was mainly present in the extracellular compartment. In comparison, the fraction of IGFBP-2 secreted was less abundant whereas the IGFBP-2 fraction in the intracellular compartment appeared stronger. In addition, analysis of the subcellular localization provided data indicating the presence of IGFBP-2 in the nucleus. Taken together these data support a role for IGFBP-2. and IGFBP-3 in the processes of growth arrest and apoptosis in lung epithelial cells upon oxidant exposure. They also suggest that distinct mechanisms may link IGFBP-2 and IGFBP-3 to the key regulators of the cell cycle. (C) 2001 Elsevier Science B.V. All rights reserved.