Potentiation of ABCA3 lipid transport function by ivacaftor and genistein
Potentiation of ABCA3 lipid transport function by ivacaftor and genistein
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DOI：
10.1111/jcmm.14397
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发表时间：
2019-08-01
影响因子：
5.3
通讯作者：
Griese, Matthias
中科院分区：
文献类型：
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作者：
Kinting, Susanna;Li, Yang;Griese, Matthias
ABCA3是一种磷脂转运蛋白，与肺表面活性物质的稳态有关，定位于肺泡II型细胞表面活性物质的储存室板层小体的界膜上。ABCA3基因突变是由表面活性物质缺乏引起的疾病的常见遗传原因，如新生儿的呼吸窘迫和儿童和成人的间质性肺疾病，目前尚无因果治疗方法。在这项研究中，我们研究了囊性纤维化跨膜电导调节器(CFTR)的两种增强剂异烟肼和金雀异黄素对ABCA3特异性脂质运输功能的影响。野生型(WT)和功能性ABCA3突变N568D、F629L、G667R、T1114M和L1580P在A549细胞中稳定表达。三维模型预测了所有五个突变体的功能损伤，这一预测得到了体外实验的证实(所有
ABCA3 is a phospholipid transporter implicated in pulmonary surfactant homoeostasis and localized at the limiting membrane of lamellar bodies, the storage compartment for surfactant in alveolar type II cells. Mutations in ABCA3 display a common genetic cause for diseases caused by surfactant deficiency like respiratory distress in neonates and interstitial lung disease in children and adults, for which currently no causal therapy exists. In this study, we investigated the effects of ivacaftor and genistein, two potentiators of the cystic fibrosis transmembrane conductance regulator (CFTR), on ABCA3-specific lipid transport function. Wild-type (WT) and functional ABCA3 mutations N568D, F629L, G667R, T1114M and L1580P were stably expressed in A549 cells. Three-dimensional modelling predicted functional impairment for all five mutants that was confirmed by in vitro experiments (all