Nature Cell Biology
1, 260 - 266 (1999)
Published online: 2 August 1999; | doi:10.1038/12971
Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory responseGillian S. Ashcroft1, 2, Xiao Yang3, Adam B. Glick4, Michael Weinstein3, John J. Letterio1, Diane E. Mizel2, Mario Anzano1, Teresa Greenwell-Wild2, Sharon M. Wahl2, Chuxia Deng3
& Anita B. Roberts11
Laboratory of Cell Regulation and Carcinogenesis, NCI, Building 41, Room C629, 41 Library Drive, MSC 5055, Bethesda, Maryland 20892-5055, USA
2
Oral Infection and Immunity Branch, NIDCR, NIH, Building 30, Bethesda, Maryland 20892-4352, USA
3
Genetics of Development and Disease Branch, NIDDK, NIH, Building 10, Bethesda, Maryland 20892, USA
4
Laboratory of Cellular Carcinogenesis & Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892,
USA
Correspondence should be addressed to Anita B. Roberts Robertsa@dce41.nci.nih.govThe generation of animals lacking SMAD proteins, which transduce signals from transforming growth factor- (TGF-), has made it possible to explore the contribution of the SMAD proteins to TGF- activity in vivo. Here we report that, in contrast to predictions made on the basis of the ability of exogenous TGF- 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-. 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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