I propose to elucidate the mechanisms that regulate vascularization during would healing. Vasculogenesis is an important event of early wound healing, delivering nutrients, oxygen and inflammatory cells (and possibly precursor stem cells) to the wound site. However, during the resolving phase of repair, most of the new vessels involute. Excessive vasculature prevents the maturation of the dermis to a relatively acellular barrier. While many groups are examining the initiating of new vessels, few are looking at the stop signals that limit the neovasculature. Previous work in my mentor's laboratory identified a class of chemokines that act as stop signals for fibroplasia during the resolving phase of wound healing. For this study, I hypothesize that these ELR-negative CXC chemokines IP-10 and/or Mig also prevent excessive vascularization. I will first verify that endothelial cell migration is inhibited as reported in the literature. Then I will identify the pathway(s) through which IP-10 and/or Mig inhibits endothelial cell migration/proliferation. I also will investigate whether the CXC chemokine receptor 3 is upregulated on microvascular endothelial cells at different stages of wound healing. Lastly, we will determine the signals that induce the production and release of IP-10 and Mig from cells during wound healing. This study will provide potential new targets to promote or limit vascular development in tissue and contribute to our ability to engineer tissues with appropriate microvasculature.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL074597-01
Application #
6692826
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Schucker, Beth
Project Start
2003-08-06
Project End
2006-08-05
Budget Start
2003-08-06
Budget End
2004-08-05
Support Year
1
Fiscal Year
2003
Total Cost
$39,700
Indirect Cost
Name
University of Pittsburgh
Department
Pathology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Yates, Cecelia C; Whaley, Diana; Kulasekeran, Priya et al. (2007) Delayed and deficient dermal maturation in mice lacking the CXCR3 ELR-negative CXC chemokine receptor. Am J Pathol 171:484-95