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-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.
Ashcroft
G S
GS
Laboratory of Cell Regulation and Carcinogenesis, NCI, Bethesda, Maryland 20892-5055, USA.
Yang
X
X
Glick
A B
AB
Weinstein
M
M
Letterio
J L
JL
Mizel
D E
DE
Anzano
M
M
Greenwell-Wild
T
T
Wahl
S M
SM
Deng
C
C
Roberts
A B
AB
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D002633:Chemotaxis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction; D012867:Skin / Q000293:injuries; D051900:Smad3 Protein; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*; D014947:Wounds and Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
D004268:DNA-Binding Proteins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta