Expression of endogenous transforming growth factor-β1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-β has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-β1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-β1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3- 10-day-old neonatal transforming growth factor-β1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-β1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-β1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-β1 null mice. Again, no impairment in healing was seen in transforming growth factor-β1 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-β1 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- β1 may actually function to increase inflammation and retard wound closure.
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