Gene delivery of a mutant TGFß3 reduces markers of scar tissue formation after cutaneous wounding.
Mol Ther
; 18(12): 2104-11, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-20736928
ABSTRACT
The transforming growth factor-ß (TGFß) family plays a critical regulatory role in repair and coordination of remodeling after cutaneous wounding. TGFß1-mediated chemotaxis promotes the recruitment of fibroblasts to the wound site and their resultant myofibroblastic transdifferentiation that is responsible for elastic fiber deposition and wound closure. TGFß3 has been implicated in an antagonistic role regulating overt wound closure and promoting ordered dermal remodeling. We generated a mutant form of TGFß3 (mutTGFß3) by ablating its binding site for the latency-associated TGFß binding protein (LTBP-1) in order to improve bioavailability and activity. The mutated cytokine is secreted as the stable latency-associated peptide (LAP)-associated form and is activated by normal intracellular and extracellular mechanisms including integrin-mediated activation but is not sequestered. We show localized intradermal transduction using a lentiviral vector expressing the mutTGFß3 in a mouse skin wounding model reduced re-epithelialization density and fibroblast/myofibroblast transdifferentiation within the wound area, both indicative of reduced scar tissue formation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cicatrización de Heridas
/
Terapia Genética
/
Factor de Crecimiento Transformador beta3
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Reino Unido