Acute stretch promotes endothelial cell proliferation in wounded healing mouse skin

• Published in: Archives of Dermatological Research Vol. 300; no. 9; pp. 495 - 504
• Main Authors: Shrader, Carl D., Ressetar, Holly G., Luo, Jia, Cilento, Eugene V., Reilly, Frank D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.10.2008; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Cell Proliferation; Dermatology; Endothelium, Vascular - cytology; Insulin - metabolism; Male; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Hairless; Original Paper; Proto-Oncogene Proteins c-akt - metabolism; Receptor, IGF Type 1 - metabolism; Regional Blood Flow - physiology; Signal Transduction - physiology; Skin - blood supply; Skin - metabolism; Stress, Mechanical; Surgical Flaps; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Wound Healing - physiology; Skin; Proliferation; Insulin; Acute stretch; Endothelium; Cell proliferation; Endothelial cell; Dermatology; Acute; Rodentia; Vertebrata; Mammalia; Mouse; Animal; Cicatrization
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s00403-008-0836-3

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.