Opposite effects of PDGF-BB and prostaglandin E1 on cell-motility related processes are paralleled by modifications of distinct actin-binding proteins.

ABSTRACT

Prostaglandin E(1) (PGE(1)) lowers dermal interstitial fluid pressure (IFP) in vivo and inhibits fibroblast-mediated collagen gel contraction in vitro. PDGF-BB, in contrast, stimulates contraction and normalizes IFP lowered as a result of anaphylaxis. Human diploid AG1518 fibroblasts expressed EP2, EP3 and IP prostaglandin receptors. The inhibitory effect of PGE(1) on contraction depended on cAMP. Short-term stimulation with PDGF-BB transiently induced formation of actin-containing membrane and circular ruffles and breakdown of stress fibers. PGE(1) had no effect on stress fibers nor did it modulate the effects of PDGF-BB. PGE(1) alone or in combination with PDGF-BB inhibited initial adhesion and spreading to collagen. PDGF-BB had no effect on adhesion but stimulated cell spreading. Two-dimensional gel electrophoresis and MALDI TOF analyses of SDS/Triton X-100-soluble proteins revealed changes in migration pattern of actin-binding proteins. Interestingly, PDGF-BB and PGE(1) affected both similar and different sets of actin-binding proteins. PDGF-BB and PGE(1) did not trans-modulate their respective effects on actin-binding proteins, cytoskeletal organization or initial adhesion. Our data show that PDGF-BB stimulates actin cytoskeleton dynamics, whereas PGE(1) inhibits processes dependent on cytoskeletal motor functions. We suggest that these different activities may partly explain the contrasting effects of PGE(1) and PDGF-BB on contraction and IFP.