SU5416 delays wound healing through inhibition of TGF-beta 1 activation.
Cancer Biol Ther
; 1(2): 121-6, 2002.
Article
em En
| MEDLINE
| ID: mdl-12170771
ABSTRACT
Angiogenesis, development of new blood vessels, is essential for wound healing and tumor growth. A potentially important side effect of anti-angiogenic therapy can be delayed wound healing. In this study we address this issue by using a novel in vivo method utilizing fibrin containing dual porous plexiglass chambers (Fibrin Z-Chambers; F-ZC) to investigate wound healing in rats administered with SU5416 (inhibitor of Flk-1 and Flt-1, at 20 mg/kg i.p.). SU5416 treated F-ZCs developed 45% less granulation tissue (p = 0.0076) and showed a 10% reduction in microvessel density (p = 0.0009) than controls treated with drug carrier alone. The granulation tissue showed distinctly decreased collagen deposition (p = 0.0006) in SU5416 treated animals that was associated with 90% reduction in active TGF-beta 1 level. We found that tissue transglutaminase (TG), a cross-linking enzyme involved in TGF-beta 1 activation and matrix stabilization, was inhibited by SU5416. These results suggest that SU5416 delays wound healing by reducing matrix synthesis and stabilization through inhibition of TGF-beta 1 activation. This study was made feasible via the development of a unique method to study anti-angiogenic compounds that provides highly reproducible and quantitative results. Further studies are needed to evaluate in vivo whether anti-angiogenic agents alter wound healing.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Cicatrização
/
Proteínas Tirosina Quinases
/
Fator de Crescimento Transformador beta
/
Inibidores da Angiogênese
/
Inibidores Enzimáticos
/
Indóis
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article