FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury

Stem Cell Reports. 2019 May 14;12(5):1041-1055. doi: 10.1016/j.stemcr.2019.04.003. Epub 2019 May 2.


Idiopathic pulmonary fibrosis is a common form of interstitial lung disease resulting in alveolar remodeling and progressive loss of pulmonary function because of chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures expressing atypical proximal airway epithelial markers replace alveolar structures, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Bronchial epithelial stem cells (BESCs) can give rise to AT2 and AT1 cells or honeycomb cysts following bleomycin-mediated lung injury. However, little is known about what controls this binary decision or whether this decision can be reversed. Here we report that inactivation of Fgfr2b in BESCs impairs their contribution to both alveolar epithelial regeneration and honeycomb cysts after bleomycin injury. By contrast overexpression of Fgf10 in BESCs enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts.

Keywords: Fgf signaling; lung fibrosis; lung regeneration; lung stem cells.

Publication types

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

MeSH terms

  • Alveolar Epithelial Cells / cytology
  • Alveolar Epithelial Cells / metabolism*
  • Animals
  • Bleomycin
  • Cell Line
  • Female
  • Fibroblast Growth Factor 10 / genetics
  • Fibroblast Growth Factor 10 / metabolism*
  • Humans
  • Lung Injury / chemically induced
  • Lung Injury / genetics
  • Lung Injury / metabolism*
  • Male
  • Mice, Knockout
  • Mice, Transgenic
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism*
  • Regeneration / genetics
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / physiology
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*


  • Fgf10 protein, mouse
  • Fibroblast Growth Factor 10
  • Bleomycin
  • Receptor, Fibroblast Growth Factor, Type 2