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Research Paper
SU5416 Delays Wound Healing Through Inhibition of TGF-b1 Activation
Zishan A. Haroon, Khalid Amin, Wilfred Saito, William Wilson, Charles S. Greenberg and Mark W. Dewhirst
volume 1 | issue 2
March/April 2002Pages: 121-127
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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 IP). 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-b1 level. We found that tissue transglutaminase (TG), a cross-linking enzyme involved in TGF-b1 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-b1 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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.