Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 5, Pages 1603-1612Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1816030116
Keywords
pneumonia; lung regeneration; Abl kinases; alveolar injury
Categories
Funding
- National Institute of Allergy and Infectious Diseases [UC6-AI058607]
- National Heart, Lung, and Blood Institute [F30HL126448, T32GM007171, 4R00HL127181]
- National Institutes of Health [DK065988, 1R01HL135239-01A1, 1K08HL130557-01A1, R01CA195549, R01AI056266]
- Cystic Fibrosis Foundation [BOUCHE15R0]
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Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be therapeutically targeted in response to infections to promote activation of progenitor cell types remains elusive. Here, we report that loss of Abl1 specifically in SCGB1A1-expressing cells leads to a significant increase in the proliferation and differentiation of bronchiolar epithelial cells, resulting in dramatic expansion of an SCGB1A1+ airway cell population that coexpresses SPC, a marker for type II alveolar cells that promotes alveolar regeneration following bacterial pneumonia. Furthermore, treatment with an Abl-specific allosteric inhibitor enhanced regeneration of the alveolar epithelium and promoted accelerated recovery of mice following pneumonia. These data reveal a potential actionable target that may be exploited for efficient recovery after pathogen-induced infections.
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