Flightless I deficiency enhances wound repair by increasing cell migration and proliferation.
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.
Cowin
A J
AJ
Child Health Research Institute, 72 King William Road, North Adelaide, South Australia.|Department of Paediatrics, University of Adelaide, South Australia.|School of Pharmacy and Medical Sciences, University of South Australia, Australia.
Adams
D H
DH
Child Health Research Institute, 72 King William Road, North Adelaide, South Australia.
Strudwick
X L
XL
Child Health Research Institute, 72 King William Road, North Adelaide, South Australia.
Chan
H
H
Child Health Research Institute, 72 King William Road, North Adelaide, South Australia.
Hooper
J A
JA
Molecular Genetics and Evolution Group and Centre for the Molecular Genetics of Development, Research School of Biological Sciences, Australian National University, Canberra, ACT, Australia.
Sander
G R
GR
Child Health Research Institute, 72 King William Road, North Adelaide, South Australia.|Department of Paediatrics, University of Adelaide, South Australia.
Rayner
T E
TE
Child Health Research Institute, 72 King William Road, North Adelaide, South Australia.
Matthaei
K I
KI
Division of Molecular Bioscience, The John Curtin School of Medical Research, Canberra, ACT, Australia.
Powell
B C
BC
Child Health Research Institute, 72 King William Road, North Adelaide, South Australia.|Department of Paediatrics, University of Adelaide, South Australia.|School of Pharmacy and Medical Sciences, University of South Australia, Australia.
Campbell
H D
HD
Molecular Genetics and Evolution Group and Centre for the Molecular Genetics of Development, Research School of Biological Sciences, Australian National University, Canberra, ACT, Australia.
D000199:Actins / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D024042:Collagen Type I / Q000032:analysis / Q000096:biosynthesis; D004847:Epithelial Cells / Q000502:physiology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000172:deficiency* / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000276:immunology; D015534:Trans-Activators; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014945:Wound Healing / Q000276:immunology / Q000502:physiology*
D000199:Actins; D000906:Antibodies; D024042:Collagen Type I; C098179:FLII protein, human; D008840:Microfilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014404:Tubulin