Balance of life and death in alveolar epithelial type II cells: Proliferation, apoptosis, and the effects of cyclic stretch on wound healing

Lynn M. Crosby, Charlean Luellen, Zhihong Zhang, Larry L. Tague, Scott E. Sinclair, Christopher M. Waters

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

After acute lung injury, repair of the alveolar epithelium occurs on a substrate undergoing cyclic mechanical deformation. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. We examined epithelial repair during cyclic stretch (CS) in a scratchwound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caused significant intercellular gap formation compared with static cells. Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier.

Original languageEnglish
Pages (from-to)L536-L546
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • Focal adhesion
  • Mechanical stretch
  • Mechanical ventilation
  • Morphometry
  • Pulmonary alveolar cells
  • Type ii pneumocytes
  • Ventilator-induced lung injury
  • Wound healing

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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