Based primarily on in vitro studies, laminin alpha1 is believed to play important roles in early lung development, yet it is not expressed in normal adult mouse or human lung. However, we recently detected laminin alpha1 expression in adult mouse lungs following bleomycin-induced lung injury.
SPECIFIC AIM 1 of this proposal is to define in vivo roles for laminin alpha1 in lung development and repair. Conventional laminin alpha1 knockout mice die at E5, prior to lung bud formation. Therefore, we will develop conditional laminin alpha1 knockout mice. With these mice and a doxycycline-inducible cre/lox system, we can obtain temporal-spatial control of laminin alpha1 expression. We will use this system to regulate laminin alpha1 expression at various stages of lung development and during bleomycin-induced lung injury. These studies will determine how the absence of laminin alpha1 affects lung development and repair. To elucidate the mechanisms by which laminins play roles in alveolar re-epithelialization following diffuse alveolar damage, SPECIFIC AIM 2 will focus on the roles of laminins-1 and -10 in epithelial cell proliferation, migration, and differentiation. Better understanding of the role of BM components like laminins in lung development and repair will enhance the ability to promote restoration of lung structure and function after diffuse alveolar damage.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
7F32HL071423-02
Application #
6619659
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Colombini-Hatch, Sandra
Project Start
2002-08-01
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$49,864
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Adair-Kirk, Tracy L; Atkinson, Jeffrey J; Kelley, Diane G et al. (2005) A chemotactic peptide from laminin alpha 5 functions as a regulator of inflammatory immune responses via TNF alpha-mediated signaling. J Immunol 174:1621-9