ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia

Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1603-1612. doi: 10.1073/pnas.1816030116. Epub 2019 Jan 17.


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.

Keywords: Abl kinases; alveolar injury; lung regeneration; pneumonia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / physiology
  • Animals
  • Bronchioles / metabolism
  • Bronchioles / physiopathology
  • Cell Differentiation / physiology
  • Cell Line
  • Female
  • Humans
  • Lung / metabolism*
  • Lung / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pneumonia, Bacterial / metabolism*
  • Pneumonia, Bacterial / physiopathology
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / physiopathology
  • Regeneration / physiology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / physiopathology
  • Stem Cells / metabolism*
  • Stem Cells / physiology
  • Uteroglobin / metabolism*


  • SCGB1A1 protein, human
  • Uteroglobin
  • Proto-Oncogene Proteins c-abl