Cystic fibrosis: an inherited disease affecting mucin-producing organs.
Cystic fibrosis: an inherited disease affecting mucin-producing organs.
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DOI：
10.1016/j.biocel.2014.03.011
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发表时间：
2014-07
影响因子：
4
通讯作者：
Thornton, David J.
中科院分区：
文献类型：
--
作者：
Ehre, Camille;Ridley, Caroline;Thornton, David J.
我们目前对囊性纤维化（CF）的理解表明，鉴于大多数粘液产生器官在囊性纤维化患者中受到影响，粘液的生物物理特性在该疾病的发病机制中发挥着相当大的作用。在这篇综述中，我们讨论了囊性纤维化跨膜电导调节器 (CFTR) 功能改变与肠道和肺部生物物理特性异常的粘液产生之间的潜在因果关系，强调了从模拟 CF 发病机制的细胞培养物和动物模型中学到的知识。类似的一系列事件，包括粘液阻塞、感染和炎症，对于所有受表面水合作用受损影响的上皮细胞来说都是常见的。因此，粘液的主要结构成分，即聚合的、形成凝胶的粘蛋白，对于疾病的发作至关重要。 CFTR 缺陷会导致上皮表面脱水、pH/电解质组成和粘蛋白浓度改变。此外，它还可以影响粘蛋白从细胞内环境到细胞外环境的转变，可能导致异常粘液凝胶的形成。虽然 HCO3− 产生缺陷长期以来一直被认为是 CF 的一个特征，但直到最近它才被认为是粘蛋白过渡阶段的关键角色。最后，我们检查了粘蛋白对 CF 痰生物物理特性的影响，并讨论了旨在清除肺部粘液的现有和新型疗法。
Our current understanding of cystic fibrosis (CF) has revealed that the biophysical properties of mucus play a considerable role in the pathogenesis of the disease in view of the fact that most mucus-producing organs are affected in CF patients. In this review, we discuss the potential causal relationship between altered cystic fibrosis transmembrane conductance regulator (CFTR) function and the production of mucus with abnormal biophysical properties in the intestine and lungs, highlighting what has been learned from cell cultures and animal models that mimic CF pathogenesis. A similar cascade of events, including mucus obstruction, infection and inflammation, is common to all epithelia affected by impaired surface hydration. Hence, the main structural components of mucus, namely the polymeric, gel-forming mucins, are critical to the onset of the disease. Defective CFTR leads to epithelial surface dehydration, altered pH/electrolyte composition and mucin concentration. Further, it can influence mucin transition from the intracellular to extracellular environment, potentially resulting in aberrant mucus gel formation. While defective HCO3− production has long been identified as a feature of CF, it has only recently been considered as a key player in the transition phase of mucins. We conclude by examining the influence of mucins on the biophysical properties of CF sputum and discuss existing and novel therapies aimed at removing mucus from the lungs.
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DOI：
10.1126/science.1223012
发表时间：
2012-08-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Button B;Cai LH;Ehre C;Kesimer M;Hill DB;Sheehan JK;Boucher RC;Rubinstein M
通讯作者：
Rubinstein M
影响因子：
4.8
作者：
Axelsson, MAB;Asker, N;Hansson, GC
通讯作者：
Hansson, GC
影响因子：
5.8
作者：
Davies, Jane C
通讯作者：
Davies, Jane C
影响因子：
5.5
作者：
Briel, M;Greger, R;Kunzelmann, K
通讯作者：
Kunzelmann, K
影响因子：
5.4
作者：
De Lisle, Robert C.;Borowitz, Drucy
通讯作者：
Borowitz, Drucy