This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project aims to define the role of the coagulation system in the inflammatory milieu of asthma. We have previously shown that fibrin, the main structural component of a blood clot, is not only present in the airways of asthmatics but also sufficient and necessary for the development of airway hyperresponsiveness in a mouse model of asthma. Airway hyperresponsiveness is a defining feature of asthma and is thought to be the result of persistent inflammation in the airways of asthmatics. Currently we are striving to link the inflammation in asthma to the formation of fibrin within airways. Interleukin-13 is a cytokine that is thought to be central in the inflamed asthmatic airway. IL-13 has many effects some of which include upregulation of plasminogen activator inhibitor type-1 (PAI-1). PAI-1 inhibits the break down of fibrin and hence increased levels of PAI-1 will promote clot or fibrin formation on the airway surface. We had previously shown that in a mouse model of asthma PAI-1 activity levels are increased. In this project we hope to link IL-13 to PAI-1 and establish the importance of intermediary steps and define how IL-13 leads to increased PAI-1 activity and ultimately fibrin formation.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR015557-07
Application #
7381078
Study Section
Special Emphasis Panel (ZRR1-RI-8 (02))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
7
Fiscal Year
2006
Total Cost
$280,989
Indirect Cost
Name
University of Vermont & St Agric College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
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Cruz, Fernanda F; Borg, Zachary D; Goodwin, Meagan et al. (2016) CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation. Stem Cells Transl Med 5:488-99
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