Incisional wound healing in transforming growth factor-beta 1 null mice

Expression of endogenous transforming growth factor-beta 1 is reduced in ma ny animal models of impaired wound healing, and addition of exogenous trans forming growth factor-beta has been shown to improve healing. To test the h ypothesis that endogenous transforming growth factor-beta 1 is essential fo r normal wound repair, we have studied wound healing in mice in which the t ransforming growth factor-beta 1 gene has been deleted by homologous recomb ination. No perceptible differences were observed in wounds made in 3-10-da y-old neonatal transforming growth factor-beta 1 null mice compared to wild -type littermates. To preclude interference from maternally transferred tra nsforming growth factor-beta 1, cutaneous wounds were also made on the back s of 30-day-old transforming growth factor-beta 1 null and littermate contr ol mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor -beta 1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta 1 null mice. Instead these wounds showed an overall red uction in the amount of granulation tissue and an increased rate of epithel ialization compared to littermate controls. Our data suggest that release o f transforming growth factor-beta 1 from degranulating platelets or secreti on by infiltrating macrophages and fibroblasts is not critical to initiatio n or progression of tissue repair and that endogenous transforming growth f actor-beta 1 may actually function to increase inflammation and retard woun d closure.