Li Danni, Han XiaoXuan, Habgood Mark, Schneider-Futschik Elena K
Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.
ACS Pharmacol Transl Sci. 2023 Feb 13;6(3):355-360. doi: 10.1021/acsptsci.2c00233. eCollection 2023 Mar 10.
In cystic fibrosis (CF) the ability of the CF transmembrane conductance regulator (CFTR) protein to mediate chloride and water transport is disrupted. While much progress has been made in CF research leading to effective treatments to improve CFTR function, including small molecule modulators, patients present with varying disease manifestations and responses to therapy. For many CF-affected organs, disease onset is known to occur during development before treatments can be administered and progresses over time leading to irreversible damage to these organs. Thus, the role of functional CFTR protein, in particular, during early development needs to be further elucidated. Studies have detected CFTR proteins at very early gestational stages and revealed temporally and spatially variable CFTR expression patterns in fetuses, suggesting a potential role of CFTR in fetal development. However, the actual mechanisms of how defective CFTR in CF results in fetal morphogenetic abnormalities are yet to be established. This review aims to summarize fetal CFTR expression patterns specifically in the lung, pancreas, and gastrointestinal tract (GIT), as compared to adult patterns. Case studies of structural abnormalities in CF fetuses and newborns and the role of CFTR in fetal development will also be discussed.
在囊性纤维化（CF）中，CF跨膜传导调节因子（CFTR）蛋白介导氯离子和水运输的能力受到破坏。虽然CF研究已取得很大进展，开发出了包括小分子调节剂在内的有效治疗方法来改善CFTR功能，但患者的疾病表现和对治疗的反应各不相同。对于许多受CF影响的器官，已知疾病在能够进行治疗之前的发育过程中就已开始，并随时间推移而进展，导致这些器官发生不可逆损伤。因此，功能性CFTR蛋白的作用，尤其是在早期发育过程中的作用，需要进一步阐明。研究已在妊娠早期阶段检测到CFTR蛋白，并揭示了胎儿中CFTR表达模式在时间和空间上的变化，这表明CFTR在胎儿发育中可能发挥作用。然而，CF中缺陷性CFTR导致胎儿形态发生异常的实际机制尚未明确。本综述旨在总结与成人模式相比，胎儿CFTR在肺、胰腺和胃肠道（GIT）中的特异性表达模式。还将讨论CF胎儿和新生儿结构异常的案例研究以及CFTR在胎儿发育中的作用。
