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Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response


The generation of animals lacking SMAD proteins, which transduce signals from transforming growth factor-β (TGF-β), has made it possible to explore the contribution of the SMAD proteins to TGF-β activity in vivo. Here we report that, in contrast to predictions made on the basis of the ability of exogenous TGF-β to improve wound healing, Smad3-null (Smad3ex8/ex8) mice paradoxically show accelerated cutaneous wound healing compared with wild-type mice, characterized by an increased rate of re-epithelialization and significantly reduced local infiltration of monocytes. Smad3ex8/ex8 keratinocytes show altered patterns of growth and migration, and Smad3ex8/ex8 monocytes exhibit a selectively blunted chemotactic response to TGF-β. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of tissue repair and in the modulation of keratinocyte and monocyte function in vivo.

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Figure 1: Smad3 disruption accelerates cutaneous wound healing.
Figure 2: Accelerated wound healing in Smad3-null mice is associated with a reduced monocytic response.
Figure 3: Addition of TGF-β1 to Smad3–/– wounds has no effect on re-epithelialization but enhances matrix production.
Figure 4: Smad3 is required for TGF-β-induced monocyte chemotaxis and TGF-β expression.
Figure 5: Smad3 deletion modulates keratinocyte proliferation and migration.


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G.S.A. was supported by a Clinician Scientist Fellowship from the Wellcome Trust. We thank L. Hansen for help with the keratinocyte assays.

Correspondence and requests for materials should be addressed to A.B.R..

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Correspondence to Anita B. Roberts.

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Ashcroft, G., Yang, X., Glick, A. et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1, 260–266 (1999).

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