Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents.
Scarring is a major cause of many clinical problems. Scar tissue interferes with growth, impairs function and is aesthetically unpleasant. However, scarring does not appear to be a problem of embryonic life. Embryonic wounds heal with a lower inflammatory and angiogenic response and have a different growth factor profile compared to adult wounds. We have used neutralising antibody to transforming growth factor-beta 1,2 (TGF-beta 1,2) to alter the growth factor profile of cutaneous wounds in adult rodents and studied the effect on scar tissue formation. This paper extends our preliminary report that neutralising antibody to TGF-beta reduces cutaneous scarring in adult rodents. To be effective, the neutralising antibody to TGF-beta needs to be administered at the time of wounding or soon thereafter. The antiscarring effects of this neutralising antibody to TGF-beta were dose dependent. Exogenous addition of neutralising antibody to TGF-beta to incisional wounds reduced the inflammatory and angiogenic responses and reduced the extracellular matrix deposition in the early stages of wound healing without reducing the tensile strength of the wounds. Importantly, the architecture of the neodermis of wounds treated with neutralising antibody to TGF-beta resembled more closely that of normal dermis compared to the unmanipulated control wounds, which healed with an abnormal neodermal architecture resulting in obvious scarring. This study suggests a novel therapeutic approach to reducing scarring in post-natal life.
Shah
M
M
Department of Cell and Structural Biology, School of Biological Sciences, University of Manchester, UK.
Foreman
D M
DM
Ferguson
M W
MW
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D008297:Male; D009500:Neutralization Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
D000906:Antibodies; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D003094:Collagen