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Title: The use of a whole animal biophotonic model as a screen for the angiogenic potential of estrogenic compounds

Author
item YOUNGBLOOD, RAMEY - Mississippi State University
item MCGEE, MARCUS - University Of Idaho
item FEUGANG, JEAN - Mississippi State University
item WILLARD, SCOTT - Mississippi State University
item RYAN, PETER - Mississippi State University

Submitted to: International Journal of Medical Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/25/2014
Publication Date: 4/7/2014
Citation: Youngblood, R.C., Mcgee, M., Feugang, J.M., Willard, S.T., Ryan, P.L. 2014. The use of a whole animal biophotonic model as a screen for the angiogenic potential of estrogenic compounds. International Journal of Medical Sciences. 11(6):545-553.

Interpretive Summary: Wound healing is an organized response to organ or tissue injury. Wound healing models are useful tools for understanding tissue repair and regeneration processes such as angiogenesis; which is the formation of capillary sprouts from pre-existing blood vessels. Vascular endothelial growth factor (VEGF) is essential for normal vascular (blood vessel) growth and development during wound repair. The current study was designed to determine whether a new transgenic mouse model for VEGF receptor (VEGF-R) would be a useful tool for evaluating hormone (estrogen) interactions during wound healing. Using a real-time imaging technology coupled with this new mouse model, we observed changes in VEGFR-2 activity associated with the dermal wound healing process and were able to be measure these via photonic (light) imaging which was an indicator of VEGF-R activity. However, responses to hormone treatments were not significant, therefore this model may have limited usefulness as a screening model for hormone (estrogenic) compounds.

Technical Abstract: Vascular endothelial growth factor (VEGF) is essential for normal vascular growth and development during wound repair. VEGF is estrogen responsive and capable of regulating its own receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). Several agricultural pesticides (e.g., methoxychlor) have estrogenic potential that can initiate inappropriate physiological responses in estrogenic-sensitive tissues following exposure in vivo. Thus, the current study was designed to determine whether the VEGFR-2-Luciferase (Luc) reporter transgenic mouse is a useful model for evaluating estrogenic tendencies of methoxychlor by monitoring wound healing via VEGFR-2-mediated gene expression using bioluminescence and real-time imaging technology. VEGFR-2-Luc gene activity peaked by d 7 (P<0.001) in all groups but was not different (P>0.05) between control and estrogen/methoxychlor exposed mice. Changes in VEGFR-2-Luc gene activity associated with the dermal wound healing process were able to be measured via photonic emission. The increase in vasculature recruitment and formation is paralleled by the increase of VEGFR-2-Luc activity with a peak on day 7. However, estrogen/methoxychlor did not significantly alter wound healing mediated VEGFR-2-Luc gene expression patterns compared to controls. This suggests that the VEGFR-2-Luc transgenic mouse wound model tested in this study may not be optimal for use as a screen for the angiogenic potential of estrogenic compounds.