RT Journal Article
SR Electronic
T1 Late Breaking Abstract - WNT/ß-catenin signaling induces cellular senescence in lung alveolar epithelial cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA4122
DO 10.1183/13993003.congress-2019.PA4122
VO 54
IS suppl 63
A1 Mareike Lehmann
A1 Kathrin Mutze
A1 Qiangjiang Hu
A1 Melanie Königshoff
YR 2019
UL http://erj.ersjournals.com/content/54/suppl_63/PA4122.abstract
AB Introduction: Idiopathic pulmonary fibrosis (IPF) is a devastating, age-related lung disease with limited therapeutic options. Several hallmarks of aging such as cellular senescence are present in disease along with the aberrant activation of developmental pathways such as WNT. How the WNT pathway influences cellular senescence and how this contributes to IPF pathogenesis mechanistically, however, remains unknown. Here, we characterized the phenotype of alveolar epithelial cells of aged mice and assessed the contribution of WNT signaling on cellular senescence.Methods: Primary alveolar epithelial cells were isolated from young and old (3/18 months) mice. Cellular composition of lungs was assessed by FACS and characterization of epithelial cells was performed by qPCR. Chronic WNT3A treatment was used to simulate increased WNT activity in pulmonary fibrosis. Cellular senescence was monitored by qPCR and senescence-associated ß-Galactosidase activity.Results: Lungs from aged mice contained less epithelial (EpCAM+) and more inflammatory (CD45+) cells. Isolated alveolar epithelial cells showed decreased expression of the alveolar epithelial type (AT)II cell marker Surfactant Protein C and its transcription factor Nkx2.1 along with increased expression of the AT1 cell marker Hopx. Profiling of WNT signaling suggested a difference in gene expression of different WNT ligands. Chronic WNT activation induced cellular senescence in alveolar epithelial cells.Conclusions: These results show that aged alveolar epithelial cells differ phenotypically from young cells. The WNT ligand expression changes with age and chronic WNT activation drives cellular senescence, likely contributing to tissue dysfunction.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA4122.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).