TGF-beta 1 accelerates wound healing: reversal of steroid-impaired healing in rats and rabbits.
TGF-beta modulates events of normal wound healing through multiple pathways that influence cell infiltration, proliferation, angiogenesis, extracellular matrix synthesis and remodeling. The effects of topically applied TGF-beta 1 on wound healing in two models of healing were evaluated when the healing response was impaired by the administration of methylprednisolone to rats or rabbits. TGF-beta 1 increased the healing of linear incision wounds on rats, as measured by breaking strength, to that of normal rats. Full thickness open wounds were also created on the inner ears of rabbits to simulate a non-contracting wound with limited blood supply. Healing was further impaired by the administration of methylprednisolone. The single application of TGF-beta 1 improved the healing of open wounds. TGF-beta 1 stimulated increased granulation tissue formation, as well as reepithelialization. The amount of granulation tissue and epithelialization were similar to wounds from normal-healing control rabbits. The delayed healing caused by methylprednisolone permitted the evaluation of multiple applications of TGF-beta 1 to wounds. Two applications of TGF-beta 1 spaced 7 days apart further improved the healing response when compared to a single application. Thus, single or multiple topical applications of TGF-beta 1 reversed impaired healing conditions secondary to methylprednisolone when used on incisional or open wounds. These observations support the hypothesis that growth factors, such as TGF-beta 1, may be useful as accelerators of wound repair in patients with impaired healing conditions.
Beck
L S
LS
Inflammation, Bone and Connective Tissue Research, Developmental Biology, Genentech Inc., South San Francisco, CA 94080.
Deguzman
L
L
Lee
W P
WP
Xu
Y
Y
McFatridge
L A
LA
Amento
E P
EP
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D008297:Male; D008775:Methylprednisolone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D016212:Transforming Growth Factor beta; D008775:Methylprednisolone