Acute stretch promotes endothelial cell proliferation in wounded healing mouse skin.
We have developed a novel in vivo model utilizing acute stretch to investigate endothelial cell proliferation as a marker of vascular growth in healing mouse skin. This study is a follow-up to ones revealing immediate stretch improves blood flow, decreases total tissue necrosis, and induces tissue insulin transcription. Dorsal distally based flaps of skin were stretched for 3 min using linear (skin hook) plus hemispherical load cycling (inflated subcutaneous silicone catheter). Unstretched, wounded skin along the back and sternum served as postoperative controls. Laser Doppler flowmetry demonstrated a threefold increase in flap perfusion at postoperative day 7. A stretch-induced sixfold increase in endothelial cell mitogenesis accompanied enhancements in blood flow and extracorporal wound healing over the sternum. Western blots revealed up-regulation/activation of insulin and mitogenic signaling intermediates in stretched skin. Activated insulin and insulin growth factor receptors (pIR/pIGFR), protein kinase B (Akt, pAkt), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (flk-1) were among the identified stretch-responsive intermediates. These results indicate the benefits of acute stretch are mediated through enhanced vascularity as evidenced by endothelial cell mitogenesis and up-regulation/activation of insulin and key angiogenic effectors in dorsal distally based skin flaps.
Shrader
Carl D
CD
Department of Neurobiology and Anatomy, School of Medicine, West Virginia University, Morgantown, WV, 26506-9128, USA. cshrader@hsc.wvu.edu
Ressetar
Holly G
HG
Luo
Jia
J
Cilento
Eugene V
EV
Reilly
Frank D
FD
D000818:Animals; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000166:cytology*; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000378:metabolism; D013314:Stress, Mechanical; D013524:Surgical Flaps; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; D017526:Receptor, IGF Type 1; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt