Human fetal skin fibroblast migration stimulated by the autocrine growth factor bFGF is mediated by phospholipase A(2) via arachidonic acid without the involvement of pertussis toxin-sensitive G-protein.
We reported previously that human fetal skin fibroblast migration into a denuded area was stimulated by an autocrine factor, basic fibroblast growth factor (bFGF). Since the signal transduction pathway of this migration is unknown, we attempted to clarify it by comparing this fibroblast migration with a previously reported bovine endothelial cell migration into a wounded area stimulated by an addition of bFGF, in which the bFGF signal was mediated by phospholipase A(2)-coupled G-protein and phospholipase A(2) (PLA(2)) via arachidonic acid. Our study demonstrated that pertussis toxin, a specific inhibitor of PLA(2)-coupled G-protein, did not suppress human fetal skin fibroblast migration, but 2-(p-amylcinnamyl)amino-4-chlorobensoic acid (ONO-RS-082), a PLA(2) inhibitor, did. Since ONO-RS-082 is a non-specific PLA(2) inhibitor, a cytoplasmic, Ca-dependent PLA(2) (cPLA(2)) inhibitor, AACOCF3, was examined. AACOCF3 suppressed cell migration in certain concentrations. The PLA(2) inhibitor-suppressed cell migration was restored by adding arachidonic acid, and cell migration suppressed by anti-bFGF antibodies was restored by adding arachidonic acid. In addition, pertussis toxin did not suppress arachidonic acid release, which shows an action of PLA(2), but AACOCF3 did. These results indicate that human fetal skin fibroblast migration stimulated by an autocrine factor, bFGF, was mediated by PLA(2) via arachidonic acid without the involvement of PLA(2)-coupled G-protein.
Kondo
H
H
Department of Cell Recognition, Tokyo Metropolitan Institute of Gerontology, Japan. hkondo@center.tmig.or.jp
Yonezawa
Y
Y
D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002723:Chlorobenzoates; D002934:Cinnamates / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology / Q000196:embryology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D062367:ortho-Aminobenzoates
D062365:Aminobenzoates; D000906:Antibodies; D001095:Arachidonic Acids; D002723:Chlorobenzoates; D002934:Cinnamates; D010566:Virulence Factors, Bordetella; D062367:ortho-Aminobenzoates; C081565:arachidonyltrifluoromethane; D016222:Fibroblast Growth Factor 2; D016718:Arachidonic Acid; C060048:2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid; D037342:Pertussis Toxin; D010741:Phospholipases A; D020962:Heterotrimeric GTP-Binding Proteins