REGULATION OF ANGIOGENESIS FACTORS BY ULTRAVIOLET RADIATION OR HYDROGEN PEROXIDE IN THE EPIDERM IN VITRO SKIN EQUIVALENT.

• TR Number: 289
• Authors: Last, T.J., Kubilus, J., Klausner, M., Sheasgreen, J. and Hayden, P. Mattek Corp., Ashland, MA.
• Materials Tested: AG1478, H2O2, TGFa

Vascular endothelial growth factors (VEGF) released by epidermis in response to environmental stimuli modulate new blood vessel growth (angiogenesis), a critical step in skin tumor progression and metastasis. Placenta growth factor (PlGF), a related angiogenic member of the VEGF family, is also expressed by epidermal keratinocytes. In order to evaluate the relative importance of VEGF and PlGF in mediating angiogenic processes in epidermis, in the present work the expression of these factors was evaluated in the EpiDerm in vitro human skin equivalent after treatment with ultraviolet radiation (UVR) or H2O2. At various times after treatment, VEGF and PlGF expression were evaluated by RT-PCR and ELISA. To examine the role of EGR receptor (EGFr) signaling in mediating expression of VEGF and PlGF, the EGFr tyrosine kinase inhibitor AG1478 was utilized.