|Ryan, P - MISS. STATE UNIV.|
|Youngblood, R - MISS. STATE UNIV.|
|Harvill, J - MISS. STATE UNIV.|
|Willard, S - MISS. STATE UNIV.|
Submitted to: Annals of the New York Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 20, 2005
Publication Date: May 1, 2005
Citation: Ryan, P.L., Youngblood, R.C., Harvill, J., Willard, S.T. 2005. Photonic Monitoring in Real-time of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Gene Expression Under Relaxin-induced Conditions in a Novel Murine Wound Model. Annals of the New York Academy of Sciences. 1041:1-17. Interpretive Summary: Rapid wound-healing, particularly in combat environments, is very desirable from a clinical perspective as it reduces the risk of infection and speeds recovery of the patient. Thus, the object of this study was to investigate the role of the hormone relaxin, a potent stimulator of vascular growth and development in reproductive tissue, on rate of vascular development during healing of dermal wounds using the transgenic vascular endothelial growth factor receptor 2-luc (VEGF2-lux) mouse model. The study observed that while measuring rate of wound healing using this mouse model was possible, relaxin had little or no effect on the wound-healing process. Biophotonic imaging and transgenic mouse models with luc reporter genes provides very useful and physiologically relevant tools for monitoring gene expression in normal, tumorigenic and tissue undergoing wound repair.
Technical Abstract: Relaxin is known to promote vascular endotheilial growth factor (VEGF) expression in reproductive tissue and successful wound-healing is dependent upon good vascularization of wound sites, a process that relaxin may facilitate. Thus, the objective of this study was to evaluate the efficacy of relaxin on development of vascular tissue at wound sites in a novel VEGF receptor 2-luc (VEGFR2-luc) transgenic mouse wound model by monitoring rate of VEGFR2-luc-mediated gene expression using bioluminescence and real time imaging. To this end, 12 FVB/N VEGFR2-luc transgenic male mice were assigned to treatments (6/group); saline alone or relaxin (1µg/6hr/14 d) administered i.p. On d 0, a set of full-thickness wounds (6 mm punch) were generated under anesthesia on the dorsal aspect of each mouse. Photonic emissions were recorded (5 min collection of photons) from wound sites 10 min after administration of luciferin (150 mg/kg i.p.) on d 0, and d 1, 2, 4, 7, 9, 11, and 14 post-wounding to quantify luciferase activity using an IVIS 100TM biophotonic imaging system. Animals were sacrificed (3/group) on d 7 or 14, and wound tissue specimens recovered for molecular and histological analyses. While photonic emission from wound sites increased (P<0.001) over time with peak values obtained by d 7, there was no significant (P>0.05) effect of relaxin treatment on VEGFR2-luc gene expression at wound sites. Whereas measuring relaxin’s effect on angiogenesis indirectly via the VEGFR2 model was not successful, photonic imaging provides an exciting new tool using alternative models (i.e., VEGF-luc mouse) to study relaxin-induced gene expression in normal or tumorigenic tissues in real-time.