The integrin αv-TGFß signaling axis is necessary for epidermal proliferation during cutaneous wound healing.
Cell Cycle
; 15(15): 2077-86, 2016 Aug 02.
Article
en En
| MEDLINE
| ID: mdl-27295308
ABSTRACT
Proliferation and migration of epidermal keratinocytes are essential for proper cutaneous wound closure after injury. αv integrins and several of their ligands-vitronectin, TGFß and thrombospondin-are up-regulated in healing wounds. However, the role of αv integrins in wound re-epithelialization is unknown. Here, we show that genetic depletion or antibody-mediated blockade of pan-integrin αv, or the specific heterodimer αvß6, in keratinocytes limited epidermal proliferation at the wound edge and prevented re-epithelialization of wounded human organotypic skin both in vivo and in vitro. While we did not observe a migration defect upon αv blockade in vivo, αv was necessary for keratinocyte migration over longer distances in organotypic skin. Integrin αv is required for local activation of latent TGFß, and the wound healing defect in the setting of integrin αv loss was rescued by exogenous, active TGFß, indicating that the αv-TGFß signaling axis is a critical component of the normal epidermal wound healing program. As chronic wounds are associated with decreased TGFß signaling, restoration of TGFß activity may have therapeutic utility in some clinical settings.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cicatrización de Heridas
/
Transducción de Señal
/
Factor de Crecimiento Transformador beta
/
Integrina alfaV
/
Epidermis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
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Male
/
Newborn
Idioma:
En
Revista:
Cell Cycle
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos