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

@article{Ashcroft1999MiceLS,
  title={Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response},
  author={G. Ashcroft and Xiao Yang and A. Glick and M. Weinstein and J. Letterio and D. Mizel and M. Anzano and T. Greenwell‐Wild and S. Wahl and C. Deng and A. Roberts},
  journal={Nature Cell Biology},
  year={1999},
  volume={1},
  pages={260-266}
}
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… Expand
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References

SHOWING 1-10 OF 43 REFERENCES
Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF‐β
TLDR
The data suggest that SMAD3 has an important role in TGF‐β‐mediated regulation of T cell activation and mucosal immunity, and that the loss of these functions is responsible for chronic infection and the lethality of Smad3‐null mice. Expand
Targeted Disruption of Smad3 Reveals an Essential Role in Transforming Growth Factor β-Mediated Signal Transduction
TLDR
A role for Smad3 in mediating the antiproliferative effects of TGF-β is established and smad3 is implicate as a potential effector for T GF-β in modulating immune system function. Expand
Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells
TLDR
It is shown that the expression of Smad3, but not its close relative, Smad2, is down-regulated by TGF-β mediated signals themselves in human lung epithelial cells, and this down-regulation does not appear to result from shortening of the half-life ofSmad3 mRNA. Expand
Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3.
TLDR
It is demonstrated that primary human skin fibroblasts express Smads, a novel family of signaling molecules, in vitro in the absence of TGF-beta, and that Smad 7 may be involved in autocrine negative feedback in the regulation of COL1A2 promoter activity by T GF-beta. Expand
Estrogen accelerates cutaneous wound healing associated with an increase in TGF-β1 levels
TLDR
It is reported that aging in healthy females was associated with a reduced rate of cutaneous wound healing, but an improved quality of scarring both microscopically and macroscopically, and with reduced levels of transforming growth factor-β1 immuno staining and steady-state mRNA in the wound. Expand
Transforming growth factor‐β: activity and efficacy in animal models of wound healing
  • A. Roberts
  • Medicine
  • Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
  • 1995
TLDR
Both topical and systemic administration of TGF‐β have been shown to improve healing in a variety of animal models of both normal and impaired healing at dermal as well as nondermal sites such as bone, intestine, the eye, or the mouth. Expand
Transforming growth factor βs and wound healing
TLDR
Evidence for the role of TGFβ superfamily members in wound healing and how modulation of T GFβ levels can prevent scarring and fibrosis are summarized. Expand
Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor.
TLDR
It is suggested that macrophages might normally act as an intermediate in the induction of procollagen synthesis in fibroblasts of PDGF-treated wounds and that TGF-beta might bypass the macrophage through its capacity to stimulate directly new synthesis of Procollagen type I in fib roblasts. Expand
Transforming growth factor beta-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells.
TLDR
Drosophila Mad proteins are stably expressed at controlled levels in epithelial cells using a novel approach that combines highly efficient retroviral gene transfer and quantitative cell sorting and it is shown that upon TGF-beta treatment Smad3 becomes rapidly phosphorylated at the SSVS motif at its very C terminus. Expand
Smad3 Mutant Mice Develop Metastatic Colorectal Cancer
TLDR
The cloning and targeted disruption of the mouse Smad3 gene is reported, which directly implicate TGFbeta signaling in the pathogenesis of colorectal cancer and provides a compelling animal model for the study of human coloreCTal cancer. Expand
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