Fibulin-5 promotes wound healing in vivo.
BACKGROUND
Fibulin-5 is a recently discovered multifunctional extracellular matrix protein that mediates endothelial cell adhesion through integrin ligation, regulates cell growth and motility in a context-specific manner, and prevents elastinopathy in vivo. Because fibulin-5 expression is induced dramatically in endothelial and smooth muscle cells in response to mechanical injury, my colleagues and I studied its role in dermal wound healing.


METHODS
We have used a gene therapy approach that used retroviral gene transfer to deliver fibulin-5 to the dermal wound milieu. Surgical generation of rabbit ear full-thickness dermal ulcers was performed in six female New Zealand white rabbits (6 months old). Wounds were injected with retrovirus containing either sense or antisense fibulin-5 or control vectors. Wounds were harvested on postwounding day 8 and analyzed by confocal microscopy, in situ hybridization, and histology.


RESULTS
We report that fibulin-5 promotes wound healing in vivo. Wounds infected with fibulin-5 showed a considerable net increase (approximately 50%) in both newly formed granulation tissue volume and wound closure. Fibulin-5 expression stimulated substantial expression of collagen in dermal wounds.


CONCLUSIONS
Taken together, our findings provide the first known example of overexpression of one extracellular matrix protein (fibulin-5) enhancing expression of another (type I collagen) in vivo. Our findings also demonstrate a novel role for fibulin-5 and suggest that altering extracellular matrix protein production through gene therapy may provide a novel means to promote wound healing.
Lee
Michael J
MJ
Division of Plastic and Reconstructive Surgery, Department of Surgery, Northwestern University, Chicago, IL, USA.
Roy
Nakshatra K
NK
Mogford
Jon E
JE
Schiemann
William P
WP
Mustoe
Thomas A
TA
D000818:Animals; D016375:Antisense Elements (Genetics); D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006097:Granulation Tissue / Q000502:physiology; D018613:Microscopy, Confocal; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*
D016375:Antisense Elements (Genetics); D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D011994:Recombinant Proteins; D003094:Collagen