Lung Injury Induces Alveolar Type 2 Cell Hypertrophy and Polyploidy with Implications for Repair and Regeneration

Anthea Weng, Mariana Maciel Herrerias, Satoshi Watanabe, Lynn C. Welch, Annette S. Flozak, Rogan A. Grant, Raul Piseaux Aillon, Laura A. Dada, SeungHye Han, Monique E Hinchcliff, Alexander V. Misharin, G. R.Scott Budinger, Cara J. Gottardi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Epithelial polyploidization after injury is a conserved phenomenon recently shown to improve barrier restoration during wound healing. Whether lung injury can induce alveolar epithelial polyploidy is not known. We show that bleomycin injury induces alveolar type 2 cell (AT2) hypertrophy and polyploidy. AT2 polyploidization is also seen in short term ex vivo cultures, where AT2-to-AT1 transdifferentiation is associated with substantial binucleation due to failed cytokinesis. Both hypertrophic and polyploid features of AT2 cells can be attenuated by inhibiting the integrated stress response using the small molecule ISRIB. These data suggest that AT2 hypertrophic growth and polyploidization may be a feature of alveolar epithelial injury. Because AT2 cells serve as facultative progenitors for the distal lung epithelium, a propensity for injury-induced binucleation has implications for AT2 selfrenewal and regenerative potential upon reinjury, which may benefit from targeting the integrated stress response.

Original languageEnglish (US)
Pages (from-to)564-576
Number of pages13
JournalAmerican journal of respiratory cell and molecular biology
Volume66
Issue number5
DOIs
StatePublished - May 2022

Keywords

  • alveolar epithelial cell
  • cytokinesis
  • hypertrophy
  • integrated stress response
  • polyploidy

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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