BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance.

Autor:	Donoghue LJ; 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., Markovetz MR; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Morrison CB; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Chen G; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., McFadden KM; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Sadritabrizi T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Gutay MI; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Kato T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Rogers TD; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Snead JY; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Livraghi-Butrico A; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Button B; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Ehre C; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.; Division of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Grubb BR; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States., Hill DB; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, United States., Kelada SNP; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2023 Dec 01; Vol. 325 (6), pp. L765-L775. Date of Electronic Publication: 2023 Oct 17.
DOI:	10.1152/ajplung.00390.2022
Abstrakt:	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 Bpifb1/Lplunc1 as a regulator of airway MUC5B protein levels using genetic approaches. Here, we show that BPIFB1 is required for effective MCC in vivo using Bpifb1 knockout (KO) mice. Reduced MCC in Bpifb1 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. NEW & NOTEWORTHY 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.
Databáze:	MEDLINE
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