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Articles in PresS, published online ahead of print December 20, 2001
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00148.2001
Submitted on April 26, 2001
Accepted on December 18, 2001
1 Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Research Service, Omaha VA Medical Center, Omaha, NE, USA
2 Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
3 Research Service, Omaha VA Medical Center, Omaha, NE, USA
* To whom correspondence should be addressed. E-mail: jspurzem{at}unmc.edu.
Bronchial epithelial cell migration is required for the repair of damaged airway epithelium. We hypothesized that bronchial epithelial cell migration during wound repair is influenced by cAMP and the activity of its cyclic nucleotide dependent protein kinase, PKA. We found that when confluent monolayers of bronchial epithelial cells are wounded, an increase in PKA activity occurs. Augmentation of PKA activity with a cell permeable analog of cAMP, dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), isoproterenol, or a phosphodiesterase inhibitor accelerated migration of normal bronchial epithelial cells in in vitro wound closure assays and Boyden chamber migration assays. A role for PKA activity was also confirmed with a PKA inhibitor, KT5720, which reduced stimulated migration. Augmentation of PKA activity reduced the levels of active Rho and the formation of focal adhesions. These studies suggest PKA activation modulates Rho activity, migration mechanisms and thus bronchial epithelial repair mechanisms.
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