Loss of Smad3 modulates wound healing.
TGF-beta plays a central and critical role in tissue repair. The recent identification of TGF-beta signal transduction pathways involving Smad proteins has now made it possible to explore their contribution to the activities of TGF-beta in vivo. Both Smad3 and its closely related homolog Smad2 act as latent nuclear transcriptional activators and mediate intracellular signaling by TGF-betas and activin, each of which regulates cellular functions pivotal to cutaneous wound healing. Mice null for Smad3 (Smad3(ex8/ex8)) survive into adulthood and show accelerated cutaneous wound healing characterized by an increased rate of re-epithelialization and a reduced local inflammatory infiltrate. These data implicate Smad3 in specific pathways of tissue repair and suggest that it could be a target for the development of therapeutic strategies to modulate wound healing.
Ashcroft
G S
GS
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Roberts
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AB
D000818:Animals; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta