Abstract
The generation of animals lacking SMAD proteins, which transduce signals from transforming growth factor-beta (TGF-beta), has made it possible to explore the contribution of the SMAD proteins to TGF-beta activity in vivo. Here we report that, in contrast to predictions made on the basis of the ability of exogenous TGF-beta 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-beta. 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Cells / cytology
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Bone Marrow Cells / physiology
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Cell Adhesion
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Cell Division
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Cells, Cultured
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Chemotaxis
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Gene Expression Regulation
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Inflammation / genetics
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Inflammation / physiopathology*
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Keratinocytes / cytology
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Keratinocytes / physiology
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Male
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Mice
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Mice, Knockout
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Monocytes / cytology
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Monocytes / physiology
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Signal Transduction
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Skin / injuries
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Smad3 Protein
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Trans-Activators / deficiency
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Trans-Activators / genetics
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Trans-Activators / physiology*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / pharmacology
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Transforming Growth Factor beta / physiology
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Wound Healing / genetics
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Wound Healing / physiology*
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Wounds and Injuries / genetics
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Wounds and Injuries / pathology
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Wounds and Injuries / physiopathology*
Substances
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DNA-Binding Proteins
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Smad3 Protein
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Smad3 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta