Photonic monitoring in real time of vascular endothelial growth factor receptor 2 gene expression under relaxin-induced conditions in a novel murine wound model.
Relaxin is known to promote vascular endothelial growth factor (VEGF) expression in reproductive tissue, and successful wound healing depends on 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 the development of vascular tissue at wound sites in a novel VEGF receptor 2-luc (VEGFR2-luc) transgenic mouse wound model by monitoring the 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 (six per group): saline alone or relaxin (1 g/6 h/14 days) administered intraperitoneally (i.p.). On day 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 the administration of luciferin (150 mg/kg i.p.) on day 0 and on days 1, 2, 4, 7, 9, 11, and 14 postwounding to quantify luciferase activity using an IVIS 100 biophotonic imaging system. Animals were sacrificed (three per group) on day 7 or 14, and wound tissue specimens were recovered for molecular and histologic analyses. Although photonic emission from wound sites increased (P < .001) over time with peak values obtained by day 7, no significant (P > .05) effect of relaxin treatment on VEGFR2-luc gene expression was noted 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 (i.e., wound healing) or tumorigenic tissues in real time.
Ryan
Peter L
PL
Department of Animal and Dairy Sciences, College of Agriculture and Life Sciences, Mississippi State University, Mississippi State, Mississippi 39762, USA. ryan@cvm.msstate.edu
Youngblood
Ramey C
RC
Harvill
Jane
J
Willard
Scott T
ST
D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D012065:Relaxin / Q000494:pharmacology*; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects; D014947:Wounds and Injuries / Q000235:genetics* / Q000378:metabolism*
D012065:Relaxin; D040301:Vascular Endothelial Growth Factor Receptor-2