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Acute stretch promotes endothelial cell proliferation in wounded healing mouse skin

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Abstract

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.

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Acknowledgments

This research was supported by interim funds from the WVU Department of Neurobiology and Anatomy (account #: DA491030020 fund #: 12301430) and WVU College of Engineering and Mineral Resources (account #: DA310880010 fund #: 11100124).

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Authors and Affiliations

  1. Department of Neurobiology and Anatomy, School of Medicine, West Virginia University, Morgantown, WV, 26506-9128, USA

    Carl D. Shrader, Holly G. Ressetar, Eugene V. Cilento & Frank D. Reilly

  2. Department of Microbiology, Immunology and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV, 26506-9177, USA

    Jia Luo

  3. Department of Chemical Engineering, College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV, 26506-6070, USA

    Eugene V. Cilento

Authors
  1. Carl D. Shrader
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  2. Holly G. Ressetar
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  3. Jia Luo
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  4. Eugene V. Cilento
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  5. Frank D. Reilly
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Correspondence to Frank D. Reilly.

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Shrader, C.D., Ressetar, H.G., Luo, J. et al. Acute stretch promotes endothelial cell proliferation in wounded healing mouse skin. Arch Dermatol Res 300, 495–504 (2008). https://doi.org/10.1007/s00403-008-0836-3

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  • DOI: https://doi.org/10.1007/s00403-008-0836-3

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