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 Sinclair, Christopher Waters

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 1 2011

Fingerprint

Alveolar Epithelial Cells
Focal Adhesions
Wound Healing
Cell Death
Cell Proliferation
Apoptosis
Cell Movement
Cell Count
Vinculin
Acute Lung Injury
Wounds and Injuries
Cell Size
Actins
Necrosis
Epithelium

All Science Journal Classification (ASJC) codes

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

Cite this

Balance of life and death in alveolar epithelial type II cells : Proliferation, apoptosis, and the effects of cyclic stretch on wound healing. / Crosby, Lynn M.; Luellen, Charlean; Zhang, Zhihong; Tague, Larry L.; Sinclair, Scott; Waters, Christopher.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 301, No. 4, 01.10.2011.

Research output: Contribution to journalArticle

@article{730f82fbea074b028cc83c5b594a5567,
title = "Balance of life and death in alveolar epithelial type II cells: Proliferation, apoptosis, and the effects of cyclic stretch on wound healing",
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.",
author = "Crosby, {Lynn M.} and Charlean Luellen and Zhihong Zhang and Tague, {Larry L.} and Scott Sinclair and Christopher Waters",
year = "2011",
month = "10",
day = "1",
doi = "10.1152/ajplung.00371.2010",
language = "English (US)",
volume = "301",
journal = "American Journal of Physiology - Lung Cellular and Molecular Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Balance of life and death in alveolar epithelial type II cells

T2 - Proliferation, apoptosis, and the effects of cyclic stretch on wound healing

AU - Crosby, Lynn M.

AU - Luellen, Charlean

AU - Zhang, Zhihong

AU - Tague, Larry L.

AU - Sinclair, Scott

AU - Waters, Christopher

PY - 2011/10/1

Y1 - 2011/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80053375223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053375223&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00371.2010

DO - 10.1152/ajplung.00371.2010

M3 - Article

VL - 301

JO - American Journal of Physiology - Lung Cellular and Molecular Physiology

JF - American Journal of Physiology - Lung Cellular and Molecular Physiology

SN - 1040-0605

IS - 4

ER -