Activation of protein kinase A accelerates bovine bronchial epithelial cell migration.
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, protein kinase A (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, 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, KT-5720, which reduced stimulated migration. Augmentation of PKA activity reduced the levels of active Rho and the formation of focal adhesions. These studies suggest that PKA activation modulates Rho activity, migration mechanisms, and thus bronchial epithelial repair mechanisms.
Spurzem
John R
JR
Department Of Veterans Affairs Medical Center, Omaha, Nebraska 68105, USA. jspurzem@unmc.edu
Gupta
Jitendrakumar
J
Veys
Thomas
T
Kneifl
Kristen R
KR
Rennard
Stephen I
SI
Wyatt
Todd A
TA
D000818:Animals; D001980:Bronchi / Q000166:cytology; D001993:Bronchodilator Agents / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology* / Q000201:enzymology
D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol