Loss of Smad3 modulates wound healing

• Published in: Cytokine & growth factor reviews Vol. 11; no. 1; pp. 125 - 131
• Main Authors: Ashcroft, Gillian S, Roberts, Anita B
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2000
• Subjects: Animals; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Humans; Inflammation; Keratinocytes - drug effects; Keratinocytes - metabolism; Mice; Signal Transduction; SMAD; Smad2 Protein; Smad3 Protein; TGF- β signaling; Trans-Activators - drug effects; Trans-Activators - genetics; Trans-Activators - metabolism; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; transforming growth factor-^b; Wound healing; Wound Healing - drug effects; Wound Healing - physiology; Inflammation; Wound healing; SMAD; TGF- β signaling
• ISSN: 1359-6101
• DOI: 10.1016/S1359-6101(99)00036-2

TGF-β plays a central and critical role in tissue repair. The recent identification of TGF-β signal transduction pathways involving Smad proteins has now made it possible to explore their contribution to the activities of TGF-β in vivo. Both Smad3 and its closely related homolog Smad2 act as latent nuclear transcriptional activators and mediate intracellular signaling by TGF-βs 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.