Exogenous addition of neutralising antibody to
transforming growth factor-beta 1,2 to cutaneous
wounds in adult rodents reduces
scarring. Three
isoforms of
transforming growth factor-beta (1, 2 and 3) have been identified in mammals. We investigated the
isoform/
isoforms of
TGF-beta responsible for cutaneous
scarring by: (i) reducing specific endogenous
TGF-beta isoforms by exogenous injection of
isoform specific neutralising
antibodies; and (ii) increasing the level of specific
TGF-beta isoforms by exogenous infiltration into the
wound margins. Exogenous addition of neutralising antibody to
TGF-beta 1 plus neutralising antibody to
TGF-beta 2 reduced the monocyte and macrophage profile, neovascularisation,
fibronectin,
collagen III and
collagen I deposition in the early stages of wound healing compared to control
wounds. Treatment with neutralising
antibodies to TGF-betas 1 and 2 markedly improved the architecture of the neodermis to resemble that of normal dermis and reduced
scarring while the control
wounds healed with
scar formation. Exogenous addition of neutralising antibody to
TGF-beta 1 alone also reduced the monocyte and macrophage profile,
fibronectin,
collagen III and
collagen I deposition compared to control
wounds. However, treatment with neutralising antibody to
TGF-beta 1 alone only marginally reduced
scarring. By contrast,
wounds treated with neutralising antibody to
TGF-beta 2 alone did not differ from control
wounds. Interestingly, exogenous addition of the
TGF-beta 3 peptide also reduced the monocyte and macrophage profile,
fibronectin,
collagen I and
collagen III deposition in the early stages of wound healing and markedly improved the architecture of the neodermis and reduced
scarring. By contrast,
wounds treated with either
TGF-beta 1 or with
TGF-beta 2 had more extracellular matrix deposition in the early stages of wound healing but did not differ from control
wounds in the final quality of
scarring. This study clearly demonstrates
isoform specific differences in the role of TGF-betas in wound healing and cutaneous
scarring.
TGF-beta 1 and
TGF-beta 2 are implicated in cutaneous
scarring. This study also suggests a novel
therapeutic use of exogenous recombinant,
TGF-beta 3 as an anti-
scarring agent.