Mesenchymal WNT-5A/5B Signaling Represses Lung Alveolar Epithelial Progenitors

Cells. 2019 Sep 25;8(10):1147. doi: 10.3390/cells8101147.


Chronic obstructive pulmonary disease (COPD) represents a worldwide concern with high morbidity and mortality, and is believed to be associated with accelerated ageing of the lung. Alveolar abnormalities leading to emphysema are a key characteristic of COPD. Pulmonary alveolar epithelial type 2 cells (AT2) produce surfactant and function as progenitors for type 1 cells. Increasing evidence shows elevated WNT-5A/B expression in ageing and in COPD that may contribute to the disease process. However, supportive roles for WNT-5A/B in lung regeneration were also reported in different studies. Thus, we explored the role of WNT-5A/B on alveolar epithelial progenitors (AEPs) in more detail. We established a Precision-Cut-Lung Slices (PCLS) model and a lung organoid model by co-culturing epithelial cells (EpCAM+/CD45-/CD31-) with fibroblasts in matrigel in vitro to study the impact of WNT-5A and WNT-5B. Our results show that WNT-5A and WNT-5B repress the growth of epithelial progenitors with WNT-5B preferentially restraining the growth and differentiation of alveolar epithelial progenitors. We provide evidence that both WNT-5A and WNT-5B negatively regulate the canonical WNT signaling pathway in alveolar epithelium. Taken together, these findings reveal the functional impact of WNT-5A/5B signaling on alveolar epithelial progenitors in the lung, which may contribute to defective alveolar repair in COPD.

Keywords: WNT signaling pathway; WNT-5A; WNT-5B; alveolar repair; chronic obstructive pulmonary disease (COPD); lung organoids; precision-cut-lung slices (PCLS).

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Alveolar Epithelial Cells / cytology*
  • Alveolar Epithelial Cells / metabolism
  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Coculture Techniques
  • Female
  • Fibroblasts / cytology
  • Humans
  • Male
  • Mice
  • Organoids / cytology*
  • Organoids / metabolism
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Up-Regulation
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway
  • Wnt-5a Protein / metabolism*


  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • Wnt5b protein, mouse