Research Paper

Poly-N-Acetyl Glucosamine Nanofibers Regulate Endothelial Cell Movement and Angiogenesis: Dependency on Integrin Activation of Ets1
John N. Vournakis^c, Juanita Eldridge^{a, b}, Marina Demcheva^c, Robin C. Muise-Helmericks<sup>a, b

a</sup>Department of Cell Biology and Anatomy, and
^bHollings Cancer Center, Medical University of South Carolina, Charleston, S.C., and
^cMarine Polymer Technologies, Inc., Danvers, Mass., USA

Address of Corresponding Author

J Vasc Res 2008;45:222-232 (DOI: 10.1159/000112544)

  Key Words

• Angiogenesis
• Cell migration
• Integrin
• Ets1
• Poly-N-acetyl glucosamine nanofiber

  Abstract

Poly-N-acetyl glucosamine (pGlcNAc) nanofiber-derived materials effectively achieve hemostasis during surgical procedures. Treatment of cutaneous wounds with pGlcNAc in a diabetic mouse animal model causes marked increases in cell proliferation and angiogenesis. We sought to understand the effect of the pGlcNAc fibers on primary endothelial cells (EC) in culture and found that pGlcNAc induces EC motility. Cell motility induced by pGlcNAc fibers is blocked by antibodies directed against V₃ and ₅₁ integrins, both known to play important roles in the regulation of EC motility, in vitroand in vivo. pGlcNAc treatment activates mitogen-activated protein kinase and increases Ets1, vascular endothelial growth factor (VEGF) and interleukin 1 (IL-1) expression. pGlcNAc activity is not secondary to its induction of VEGF; inhibition of the VEGF receptor does not inhibit the pGlcNAc-induced expression of Ets1 nor does pGlcNAc cause the activation of VEGF receptor. Both dominant negative and RNA interference inhibition of Ets1 blocks pGlcNAc-induced EC motility. Antibody blockade of integrin results in the inhibition of pGlcNAc-induced Ets1 expression. These findings support the hypothesis that pGlcNAc fibers induce integrin activation which results in the regulation of EC motility and thus in angiogenesis via a pathway dependent on the Ets1 transcription factor and demonstrate that Ets1 is a downstream mediator of integrin activation.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Robin C. Muise-Helmericks
Medical University of South Carolina, Hollings Cancer Center, Rm 320
86 Jonathon Lucas St.
Charleston, SC 29425 (USA)
Tel. +1 843 792 4760, Fax +1 843 792 5520, E-Mail musehelm@musc.edu

  Article Information

Received: March 29, 2007
Accepted after revision: August 13, 2007
Published online: December 19, 2007
Number of Print Pages : 11
Number of Figures : 6, Number of Tables : 0, Number of References : 49