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

  title={Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response},
  author={Gillian S. Ashcroft and Xiao Yang and Adam B Glick and Michael B. Weinstein and John J. Letterio and Diane E. Mizel and Mario A. Anzano and Teresa Greenwell‐Wild and Sharon M. Wahl and Chuxia Deng and Anita B. Roberts},
  journal={Nature Cell Biology},
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… 
Accelerated re-epithelialization in β3-integrin-deficient- mice is associated with enhanced TGF-β1 signaling
It is reported that mice lacking β3-integrins show enhanced wound healing with re-epithelialization complete several days earlier than in wild-type mice, and data indicate that αvβ3–integrin can suppress TGF-β1-mediated signaling, thereby controlling the rate of wound healing.
Loss of Smad3 modulates wound healing.
Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation.
Temporal smad7 transgene induction in mouse epidermis accelerates skin wound healing.
Smads in the Fibrotic Response: Findings in the Smad3 Knockout Mouse
Transforming growth factor-β (TGF-β) mediates both physiological and pathological fibrotic responses by inducing influx and activation of inflammatory cells, epithelial to mesenchymal
Functional significance of Smad2 in regulating basal keratinocyte migration during wound healing.
A crucial role is demonstrated of TGF-beta signaling mediator Smad2 in regulating keratinocyte migration and re-epithelialization during wound healing and proposed altered K16 expression affects the migration of basal keratinocytes in the K14-Smad2 mice.
Characterization of Smad3 knockout mouse derived skin cells
The findings indicate that both systemic factors and intrinsic properties of skin cells contribute to enhanced wound healing and less inflammatory reaction observed in Smad3 knock-out mice.
Impaired cutaneous wound healing in transforming growth factor‐β inducible early gene1 knockout mice
It is hypothesized that TIEG may play a role in dermal wound healing, with involvement in wound closure, contraction, and reepithelialization, and it is found that Smad7 was increased in the wounds and appeared to play a roles in this wound healing model in TIEG1–/– mice.


Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF‐β
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.
Targeted Disruption of Smad3 Reveals an Essential Role in Transforming Growth Factor β-Mediated Signal Transduction
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.
Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells
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.
Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3.
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.
Estrogen accelerates cutaneous wound healing associated with an increase in TGF-β1 levels
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.
Transforming growth factor‐β: activity and efficacy in animal models of wound healing
  • A. Roberts
  • Biology, Medicine
    Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
  • 1995
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.
Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor.
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.
Transforming growth factor beta-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells.
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.
Smad3 Mutant Mice Develop Metastatic Colorectal Cancer