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

Overview

Journal Am J Respir Cell Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2022 Feb 24

PMID 35202558

Authors

Anthea Weng

Mariana Maciel Herrerias

Satoshi Watanabe

Lynn C Welch

Annette S Flozak

Rogan A Grant

Raul Piseaux Aillon

Laura A Dada

Seung Hye Han

Monique Hinchcliff

Alexander V Misharin

G R Scott Budinger

Cara J Gottardi

Affiliations

Soon will be listed here.

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 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 self-renewal and regenerative potential upon reinjury, which may benefit from targeting the integrated stress response.

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