Functional significance of Smad2 in regulating basal keratinocyte migration during wound healing.
Members of the transforming growth factor-beta (TGF-beta) superfamily are critical regulators for wound healing. Transduction of TGF-beta signaling depends on activation of Smad2 and Smad3 by heteromeric complexes of ligand-specific receptors. Mice lacking Smad3 show accelerated wound healing, whereas the biological significance of Smad2-mediated TGF-beta signaling in wound healing remains unknown. To understand the function of Smad2 in regulating wound healing, we investigated the effect of Smad2 overexpression on epithelialization of incision wounds. Cutaneous wounds made in K14-Smad2 mice showed delayed healing. This delay in wound healing resulted from a defect in basal keratinocyte migration in K14-Smad2 mice. Instead of basal keratinocytes, the suprabasal layer of keratinocytes migrated into the wound region. Furthermore, overexpression of Smad2 activated the Smad2/Smad4 complex in keratinocytes and inhibited keratin 16 (K16) expression. As K16 functions as a critical mediator for reorganization of keratin filaments following skin injury, we propose that altered K16 expression affects the migration of basal keratinocytes in the K14-Smad2 mice. Taken together, these findings demonstrate a crucial role of TGF-beta signaling mediator Smad2 in regulating keratinocyte migration and re-epithelialization during wound healing. The K14-Smad2 transgenic mice can serve as an animal model for the investigation of TGF-beta signaling mechanism in regulating wound healing.
Hosokawa
Ryoichi
R
Center for craniofacial molecular biology, School of Dentistry, University of Southern California, Los Angeles, California 90033, USA.
Urata
Mark M
MM
Ito
Yoshihiro
Y
Bringas
Pablo
P
Chai
Yang
Y
D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D015603:Keratinocytes / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014945:Wound Healing
D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; D007633:Keratins