Nature Communications (Dec 2018)
Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice
- Laura A. Hancock,
- Corinne E. Hennessy,
- George M. Solomon,
- Evgenia Dobrinskikh,
- Alani Estrella,
- Naoko Hara,
- David B. Hill,
- William J. Kissner,
- Matthew R. Markovetz,
- Diane E. Grove Villalon,
- Matthew E. Voss,
- Guillermo J. Tearney,
- Kate S. Carroll,
- Yunlong Shi,
- Marvin I. Schwarz,
- William R. Thelin,
- Steven M. Rowe,
- Ivana V. Yang,
- Christopher M. Evans,
- David A. Schwartz
Affiliations
- Laura A. Hancock
- Department of Medicine, University of Colorado Denver, School of Medicine
- Corinne E. Hennessy
- Department of Medicine, University of Colorado Denver, School of Medicine
- George M. Solomon
- Department of Medicine, University of Alabama at Birmingham, School of Medicine
- Evgenia Dobrinskikh
- Department of Medicine, University of Colorado Denver, School of Medicine
- Alani Estrella
- Department of Medicine, University of Colorado Denver, School of Medicine
- Naoko Hara
- Department of Medicine, University of Colorado Denver, School of Medicine
- David B. Hill
- Marsico Lung Institute, University of North Carolina
- William J. Kissner
- Marsico Lung Institute, University of North Carolina
- Matthew R. Markovetz
- Marsico Lung Institute, University of North Carolina
- Diane E. Grove Villalon
- Parion Sciences, Inc
- Matthew E. Voss
- Parion Sciences, Inc
- Guillermo J. Tearney
- Wellman Center for Photomedicine and Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston
- Kate S. Carroll
- Department of Chemistry, The Scripps Research Institute
- Yunlong Shi
- Department of Chemistry, The Scripps Research Institute
- Marvin I. Schwarz
- Department of Medicine, University of Colorado Denver, School of Medicine
- William R. Thelin
- Parion Sciences, Inc
- Steven M. Rowe
- Department of Medicine, University of Alabama at Birmingham, School of Medicine
- Ivana V. Yang
- Department of Medicine, University of Colorado Denver, School of Medicine
- Christopher M. Evans
- Department of Medicine, University of Colorado Denver, School of Medicine
- David A. Schwartz
- Department of Medicine, University of Colorado Denver, School of Medicine
- DOI
- https://doi.org/10.1038/s41467-018-07768-9
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 10
Abstract
The promoter variant rs35705950 confers a gain of function to the MUC5B gene and is the dominant risk factor for idiopathic pulmonary fibrosis. Here the authors show that mice overexpressing Muc5b in distal airspaces show impaired mucociliary clearance and increased susceptibility to bleomycin-induced lung fibrosis, and that both characteristics are reduced by treatment with a mucolytic agent.
