Plastic Surgery Research Council
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INCREASED CAMP INHIBITS BASAL AND PDGF-INDUCED CELL MIGRATION IN DUPUYTREN S CONTRACTURE-DERIVED FIBROBLASTS
Presenter: Latha Satish, PhD
Co-Authors: Liu F; Kathju S
University of Pittsburgh

Dupuytren s Contracture (DC) is a fibroproliferative disorder characterized by the development of nodules in the palmar fascia which give way to the formation of restrictive fibrous cords. Multiple growth factors have been implicated in the development of DC, including platelet derived growth factor-BB (PDGF-BB) and PDGF receptor, which are shown to be elevated in DC. The present study investigated basal- and PDGF-induced cell migration in fibroblasts from patients with active DC disease (DC), from phenotypically normal palmar fascia in DC patients (PF), and from patients undergoing carpal tunnel release (CT). We explored the effect of increased cAMP in these cells on motility and on signaling kinases known to regulate cellular activity. Fibroblasts derived from six different patients were cultured, quiesced for 48h and treated with PDGF and forskolin (a known cAMP inducer). Cells were then subjected to an in-vitro wound healing scratch assay to measure cell motility into the denuded zone; photographs were taken at 0h and 48h and quantified. Total protein in DC cells was analyzed by Western blot for expression of p42/44 and p38 MAP kinases, and for activated PI3 kinase. We found higher basal motility in DC- compared to unaffected palmar fascia (PF-) and CT-derived fibroblasts. PDGF stimulated cell motility in all three populations, and addition of forskolin inhibited both basal and PDGF-induced cell migration in all three cell types. Interestingly, the inhibitory effect of forskolin on PDGF-induced cell migration was more pronounced in DC-derived fibroblasts compared to the other two cell types. Further, neither PDGF nor forskolin exposure had any effect on phosphorylation of p38 and PI3 kinase in DC-derived fibroblasts. Both forskolin and PDGF increased p42/44 MAP kinase phosphorylation, but this did not correlate with cell motility. These results for the first time examine DC fibroblast motility and suggest that cAMP may be a useful agent to modulate DC fibroblast behavior and possibly forestall disease progression and recurrence.


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