Flightless I deficiency enhances wound repair by increasing cell migration and proliferation

J Pathol. 2007 Apr;211(5):572-81. doi: 10.1002/path.2143.

Abstract

Wound healing disorders are a therapeutic problem of increasing clinical importance involving substantial morbidity, mortality, and rising health costs. Our studies investigating flightless I (FliI), a highly conserved actin-remodelling protein, now reveal that FliI is an important regulator of wound repair whose manipulation may lead to enhanced wound outcomes. We demonstrate that FliI-deficient + /- mice are characterized by improved wound healing with increased epithelial migration and enhanced wound contraction. In contrast, FliI-overexpressing mice have significantly impaired wound healing with larger less contracted wounds and reduced cellular proliferation. We show that FliI is secreted in response to wounding and that topical application of antibodies raised against the leucine-rich repeat domain of the FliI protein (FliL) significantly improves wound repair. These studies reveal that FliI affects wound repair via mechanisms involving cell migration and proliferation and that FliI might represent an effective novel therapeutic factor to improve conditions in which wound healing is impaired.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Administration, Topical
  • Animals
  • Antibodies / administration & dosage
  • Antibodies / immunology
  • Cell Division / immunology
  • Cell Division / physiology
  • Cell Movement / physiology
  • Collagen Type I / analysis
  • Collagen Type I / biosynthesis
  • Epithelial Cells / physiology
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Immunohistochemistry / methods
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Microfilament Proteins / deficiency*
  • Microfilament Proteins / immunology
  • Receptors, Cytoplasmic and Nuclear / deficiency*
  • Receptors, Cytoplasmic and Nuclear / immunology
  • Trans-Activators
  • Tubulin / metabolism
  • Up-Regulation / physiology
  • Wound Healing / immunology
  • Wound Healing / physiology*

Substances

  • Actins
  • Antibodies
  • Collagen Type I
  • FLII protein, human
  • Microfilament Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Tubulin