Opposite effects of PDGF-BB and prostaglandin E1 on cell-motility related processes are paralleled by modifications of distinct actin-binding proteins.
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.
van Wieringen
Tijs
T
Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Uppsala, Sweden.
Kimani
Stanley G
SG
Hultgård-Ekwall
Anna-Karin
AK
Forsberg
Jens
J
Reyhani
Vahid
V
Engström
Ake
A
Rubin
Kristofer
K
D000199:Actins / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005782:Gels; D020869:Gene Expression Profiling; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000199:Actins; D002148:Calmodulin-Binding Proteins; D005782:Gels; D008840:Microfilament Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D010768:Phosphoserine; D000077214:Becaplermin; D003094:Collagen; D009219:Myosin-Light-Chain Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D000527:Alprostadil