Fibulin-5 promotes wound healing in vivo.

Abstract

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. 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. 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. 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.