Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain

Christopher Waters, Ushma Savla

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The airway epithelium may be damaged by inhalation of noxious agents, in response to pathogens, or during endotracheal intubation and mechanical ventilation. Maintenance of an intact epithelium is important for lung fluid balance, and the loss of epithelium may stimulate inflammatory responses. Epithelial repair in the airways following injury must occur on a substrate that undergoes cyclic elongation and compression during respiration. We have previously shown that cyclic mechanical strain inhibits wound closure in the airway epithelium (Savla and Waters, 1998b). In this study, we investigated the stimulation of epithelial wound closure by keratinocyte growth factor (KGF) in vitro and the mechanisms by which KGF overcomes the inhibition due to mechanical strain. Primary cultures of normal human bronchial epithelial cells (NHBE) and a cell line of human airway epithelial cells, Calu 3, were grown on Silastic membranes, and a wound was scraped across the well. The wells were then exposed to cyclic strain using the Flexercell Strain Unit, and wound closure was measured. While cyclic elongation (20% maximum) and cyclic compression (;2%) both inhibited wound closure in untreated wells, treatment with KGF (50 ng/ml) significantly accelerated wound closure and overcame the inhibition due to cyclic strain. Since wound closure involves cell spreading, migration, and proliferation, we investigated the effect of cyclic strain on cell area, cell-cell distance, and cell velocity at the wound edge. While the cell area increased in unstretched monolayers, the cell area of monolayers in compressed regions decreased significantly. Treatment with KGF increased the cell area in both cyclically elongated and compressed cells. Also, when cells were treated with KGF, cell velocity was significantly increased in both static and cyclically strained monolayers, and cyclic strain did not inhibit cell migration. These results suggest that KGF is an important factor in epithelial repair that is capable of overcoming the inhibition of repair due to physiological levels of cyclic strain.

Original languageEnglish (US)
Pages (from-to)424-432
Number of pages9
JournalJournal of Cellular Physiology
Volume181
Issue number3
DOIs
StatePublished - Dec 1 1999

Fingerprint

Fibroblast Growth Factor 7
Epithelium
Wounds and Injuries
Monolayers
Repair
Elongation
Cell Movement
Epithelial Cells
Pathogens
Water-Electrolyte Balance
Intratracheal Intubation
Compaction
Artificial Respiration
Inhalation
Cells
Membranes
Respiration
Fluids
Maintenance
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain. / Waters, Christopher; Savla, Ushma.

In: Journal of Cellular Physiology, Vol. 181, No. 3, 01.12.1999, p. 424-432.

Research output: Contribution to journalArticle

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