Pulmonary Autotaxin Expression Contributes to the Pathogenesis of Pulmonary Fibrosis
Pulmonary Autotaxin Expression Contributes to the Pathogenesis of Pulmonary Fibrosis
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DOI：
10.1165/rcmb.2012-0004oc
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发表时间：
2012-11-01
影响因子：
6.4
通讯作者：
Aidinis, Vassilis
中科院分区：
文献类型：
--
作者：
Oikonomou, Nikos;Mouratis, Marios-Angelos;Aidinis, Vassilis
特发性肺纤维化（IPF）是一种慢性、进行性、纤维化的弥漫性肺病，主要发生于老年人。据报道，特发性肺纤维化患者和相应动物模型的肺泡腔中溶血磷脂酸 (LPA) 浓度增加，而 LPA 受体 1 的基因缺失或药物抑制减弱了模型疾病的发展，表明 LPA 直接参与疾病发病机制。在本报告中，在小鼠和人类纤维化肺中均检测到自分泌运动因子（ATX；ENPP2）浓度增加，该酶主要负责细胞外 LPA 的产生。支气管上皮细胞或巨噬细胞中 ATX 的基因缺失减轻了疾病的严重程度，使 ATX 成为 IPF 发病机制中的新参与者。此外，ATX 的药理学抑制作用减弱了模型疾病的发展，表明 ATX 是 IPF 的可能治疗靶点。
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic form of diffuse lung disease occurring mainly in older adults. Increased lysophosphatidic acid (LPA) concentrations have been reported in the alveolar space of both idiopathic pulmonary fibrosis patients and a corresponding animal model, whereas the genetic deletion or pharmacological inhibition of LPA receptor 1 attenuated the development of the modeled disease, suggesting a direct involvement of LPA in disease pathogenesis. In this report, increased concentrations of autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular LPA production, were detected in both murine and human fibrotic lungs. The genetic deletion of ATX from bronchial epithelial cells or macrophages attenuated disease severity, establishing ATX as a novel player in IPF pathogenesis. Furthermore, the pharmacological inhibition of ATX attenuated the development of the modeled disease, suggesting that ATX is a possible therapeutic target in IPF.