Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
Am J Physiol Lung Cell Mol Physiol. 2023 Dec 1;325(6):L765-L775. doi: 10.1152/ajplung.00390.2022. Epub 2023 Oct 17.
Airway mucociliary clearance (MCC) is required for host defense and is often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is associated with a reduction in the rate of MCC; however, how other secreted proteins impact the integrity of the mucus layer and MCC remains unclear. We previously identified the gene as a regulator of airway MUC5B protein levels using genetic approaches. Here, we show that BPIFB1 is required for effective MCC in vivo using knockout (KO) mice. Reduced MCC in KO mice occurred in the absence of defects in epithelial ion transport or reduced ciliary beat frequency. Loss of BPIFB1 in vivo and in vitro altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC. Finally, we detected colocalization of BPIFB1 and MUC5B in secretory granules in mice and the protein mesh of secreted mucus in human airway epithelia cultures. Collectively, our findings demonstrate that BPIFB1 is an important component of the mucociliary apparatus in mice and a key component of the mucus protein network. BPIFB1, also known as LPLUNC1, was found to regulate mucociliary clearance (MCC), a key aspect of host defense in the airway. Loss of this protein was also associated with altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC.
气道黏液纤毛清除（MCC）是宿主防御所必需的，而在慢性肺部疾病中往往会减弱。有效的清除取决于气道上皮和可移动的黏液层的协调作用。主要分泌性气道黏蛋白蛋白 MUC5B 和 MUC5AC 的失调与 MCC 率降低有关；然而，其他分泌蛋白如何影响黏液层的完整性和 MCC 仍然不清楚。我们之前使用遗传方法确定了[基因名称]是气道 MUC5B 蛋白水平的调节剂。在这里，我们使用[基因名称]敲除（KO）小鼠表明 BPIFB1 是体内有效 MCC 所必需的。在[基因名称] KO 小鼠中，MCC 减少发生在不存在上皮离子转运缺陷或纤毛摆动频率降低的情况下。BPIFB1 在体内和体外的缺失改变了先前与 MCC 受损相关的黏液的生物物理和生化特性。最后，我们在小鼠的分泌颗粒中和人呼吸道上皮细胞培养物的分泌黏液的蛋白质网中检测到 BPIFB1 和 MUC5B 的共定位。总的来说，我们的研究结果表明，BPIFB1 是小鼠黏液纤毛装置的重要组成部分，也是黏液蛋白网络的关键组成部分。BPIFB1，也称为 LPLUNC1，被发现调节黏液纤毛清除（MCC），这是气道宿主防御的一个关键方面。这种蛋白质的缺失也与先前与 MCC 受损相关的黏液的生物物理和生化特性的改变有关。
