Recombinant adenovirus-p21 attenuates proliferative responses associated with excessive scarring.
Wound Repair Regen
; 13(5): 480-90, 2005.
Article
em En
| MEDLINE
| ID: mdl-16176456
ABSTRACT
Excessive cutaneous scarring is an important clinical disorder resulting in adverse tissue growth and function as well as undesirable cosmetic appearance. p21WAF-1/Cip-1 is a cyclin-dependent kinase inhibitor that blocks cell cycle progression and inhibits cell proliferation. We used a recombinant adenovirus containing the human p21WAF-1/Cip-1 cDNA (rAd-p21) to evaluate proliferative responses in skin models. In vitro dose-response studies using primary human dermal fibroblasts resulted in a dose-dependent expression of p21WAF-1/Cip-1 protein and a 3- to 80-fold reduction in cell proliferation as measured by 5-bromodeoxyuridine incorporation. Further, rAd-p21 reduced type I procollagen production when compared to control virus. A rat polyvinyl alcohol sponge model was used to determine rAd-p21 effects on granulation tissue formation in vivo. Sponges pretreated with a granulation tissue stimulator, rAd-PDGF-B and subsequently rAd-p21 on a second injection, showed a p21WAF-1/Cip-1 specific dose-dependent decrease in percent granulation fill as the rAd-p21 dose increased (p < 0.001). Immunohistochemistry identified human p21WAF-1/Cip-1 expression in sponges treated with rAd-p21 5 days postinjection. Additionally, 5-bromodeoxyuridine and Ki67 staining in sponges treated with rAd-p21 showed a significant decrease in proliferation when compared to rAd-platelet-derived growth factor-B alone or vehicle control groups (p < 0.01). These data support the utility of p21WAF-1/Cip-1 in targeting hyperproliferative disorders of the skin.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Adenoviridae
/
Cicatriz
/
Inibidor de Quinase Dependente de Ciclina p21
/
Vetores Genéticos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Animals
/
Humans
Idioma:
En
Revista:
Wound Repair Regen
Assunto da revista:
DERMATOLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos