Premium
STRETCH RESPONSIVE TISSUE INSULIN INDUCED ANGIOGENESIS IN WOUNDED HEALING MOUSE SKIN
Author(s) -
Shrader Carl D.,
Ressetar Holly G.,
Luo Jia,
Cilento Eugene V.,
Reilly Frank D.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a527-a
Subject(s) - angiogenesis , vascular endothelial growth factor , growth factor , endocrinology , insulin , medicine , protein kinase b , endothelial stem cell , insulin receptor , receptor , biology , microbiology and biotechnology , signal transduction , insulin resistance , vegf receptors , biochemistry , in vitro
We developed a novel in vivo mouse model utilizing rapid stretch to investigate endothelial cell proliferation as a marker of angiogenesis. This study is a follow‐up to ones that revealed rapid stretching improves blood flow, decreases marginal tissue necrosis and induces tissue insulin transcription. Flaps of skin were stretched for 3 min using linear (skin hook) plus hemispherical load cycling (inflated subcutaneous silicone catheter). Unstretched, wounded skin served as postoperative controls. Our results demonstrated a three fold increase in flap perfusion at postoperative day 7 coincident with a six fold increase in endothelial cell mitogenesis. Western blots revealed insulin and other mitogenic signaling intermediates. 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 mediators. These findings suggest that the benefits of rapid stretch are mediated through angiogenesis as evidenced by endothelial cell mitogenesis and up‐regulation and activation of key angiogenic factors. (Supported by the Department of Neurobiology & Anatomy, WVU School of Medicine, account #: DA491030020 fund #: 12301430 and College of Engineering & Mineral Resources, West Virginia University, account #: DA310880010 fund #: 11100124)