RT Journal Article
SR Electronic
T1 Peroxisome proliferator-activated receptor ligands decrease human airway smooth muscle cell migration and extra-cellular matrix synthesis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj01450-2009
DO 10.1183/09031936.00145009
A1 Jancy Stephen
A1 Chris Delvecchio
A1 Naomi Spitale
A1 Amanda Giesler
A1 Katherine Radford
A1 Pat Bilan
A1 P. Gerard Cox
A1 John P. Capone
A1 Parameswaran Nair
YR 2012
UL http://erj.ersjournals.com/content/early/2012/05/31/09031936.00145009.abstract
AB Airway smooth muscle cells produce extracellular matrix proteins, which in turn can promote smooth muscle survival, proliferation and migration. Currently available therapies have little effect on airway smooth muscle matrix production and migration. Peroxisome-proliferator-activated receptor (PPAR) ligands are reported to decrease migration and matrix production in various cell lines. In this study, we examined the effect of PPAR ligands on human airway smooth muscle matrix production and migration. PPAR expression was examined by RT-PCR and Western blotting. Endogenous PPAR activity was examined by transfecting cells with a PPRE-luciferase reporter plasmid. We observed that human airway smooth muscle cells express α, β, and γ PPAR. A 6-fold induction of luciferase activity was observed by stimulating cells with a pan-agonist indicating endogenous PPAR activity. The PPAR-ligands ciglitazone, 15d-PGJ2, and WY-14643 decreased migration towards PDGF. This was not mediated by inhibiting Akt phosphorylation or promoting PTEN activity, but partly through COX-2 induction and PGE2 production that increased c-AMP levels in the cells. All three ligands also caused an inhibition of collagen and fibronectin secretion by cultured smooth muscle cells. We conclude that PPAR-ligands decrease human airway smooth muscle migration and matrix production and are therefore potentially useful to modulate airway remodelling.