Incisional wound healing in transforming growth factor-beta1 null mice.
Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.
Koch
R M
RM
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA.
Roche
N S
NS
Parks
W T
WT
Ashcroft
G S
GS
Letterio
J J
JJ
Roberts
A B
AB
D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D006097:Granulation Tissue / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D020123:Sirolimus / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D020123:Sirolimus