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Am J Physiol Cell Physiol (November 7, 2001). doi:10.1152/ajpcell.00419.2001
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Articles in PresS, published online ahead of print November 7, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00419.2001
Submitted on August 29, 2001
Accepted on November 3, 2001

Adenoviral gene transfer of PDGF down-regulates growth-arrest-specific (gas)gene product PDGF{alpha}R and prolongs activation of Erk and Akt/PKB

Qi-Ping Chen1 and William V Giannobile1*

1 Center for Biorestoration of Oral Health and Department of Periodontics, Prevention and Geriatrics, University of Michigan, Ann Arbor, MI, USA

* To whom correspondence should be addressed. E-mail: wgiannob{at}umich.edu.

The delivery of platelet-derived growth factor (PDGF) for tissue engineering of skin and periodontal wounds has become an active area of interest. However, little is known regarding the extended effects of PDGF on cell signaling via gene therapy and how such an approach facilitates the exiting of cells from growth arrest and entry to competence required for cell cycling. We show in vitro expression and secretion of PDGF-AA by recombinant adenovirus encoding the PDGF-A gene. The bioactive PDGF-AA protein released induces sustained down-regulation of PDGF{alpha}R that is encoded by a growth-arrest-specific (gas) gene. Ad-PDGF-A induces sustained phosphorylation of PDGF{alpha}aR as well as prolonged phosphorylation of downstream Erk 1/2 and Akt signaling pathways. Furthermore, the phosphorylation of PDGF{alpha}R is abolished by co-transducing cells with adenovirus encoding a dominant negative mutant of the PDGF-A gene that disrupts PDGF bioactivity. These findings demonstrate the prolonged effects of adenoviral delivery of PDGF and aid in the better understanding of sustained PDGF signaling.




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