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Cell. 2017 Apr 20;169(3):497-509.e13. doi: 10.1016/j.cell.2017.03.044.

Spontaneous Chitin Accumulation in Airways and Age-Related Fibrotic Lung Disease.

Author information

1
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: richard.locksley@ucsf.edu.

Abstract

The environmentally widespread polysaccharide chitin is degraded and recycled by ubiquitous bacterial and fungal chitinases. Although vertebrates express active chitinases from evolutionarily conserved loci, their role in mammalian physiology is unclear. We show that distinct lung epithelial cells secrete acidic mammalian chitinase (AMCase), which is required for airway chitinase activity. AMCase-deficient mice exhibit premature morbidity and mortality, concomitant with accumulation of environmentally derived chitin polymers in the airways and expression of pro-fibrotic cytokines. Over time, these mice develop spontaneous pulmonary fibrosis, which is ameliorated by restoration of lung chitinase activity by genetic or therapeutic approaches. AMCase-deficient epithelial cells express fibrosis-associated gene sets linked with cell stress pathways. Mice with lung fibrosis due to telomere dysfunction and humans with interstitial lung disease also accumulate excess chitin polymers in their airways. These data suggest that altered chitin clearance could exacerbate fibrogenic pathways in the setting of lung diseases characterized by epithelial cell dysfunction.

KEYWORDS:

AMCase; age-related disease; chitin; chitinase; epithelium; interleukins; interstitial lung disease; polysaccharide; pulmonary fibrosis

PMID:
28431248
PMCID:
PMC5444468
DOI:
10.1016/j.cell.2017.03.044
[Indexed for MEDLINE]
Free PMC Article

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