Abstract
Although recent clinical reports have indicated that recombinant basic fibroblast growth factor (bFGF) promotes scarless wound healing, the mechanism remains unclear. The present study was carried out to elucidate the mechanisms. The protein levels of cellular α-smooth muscle actin increased at 2-4 days after TGFβ treatment alone and at 4 to 6 days after a costimulation of bFGF and TGFβ. A spontaneous contraction of stressed myofibroblast-collagen matrix was cancelled by bFGF, which was restored under the presence of C3 exotransferase or Y27632. bFGF stimulation of myofibroblasts as well as fibroblasts elicited a transient Rac and Rho activation. bFGF promoted apoptosis of the myofibroblasts but not of the fibroblasts, even in the presence of two different inhibitors, either LY294002 or an Akt inhibitor. The present study suggests that the phosphatidylinositol-3-kinase to Akt as well as the Rho to Rho kinase signaling pathway is involved in bFGF-promoted myofibroblast apoptosis, and bFGF can promote the scarless wound healing upon the induction of apoptosis of myofibroblasts, but not fibroblasts.
MeSH terms
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Actins / metabolism
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Amides / pharmacology
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Apoptosis / drug effects*
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Cells, Cultured
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Chromones / pharmacology
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Cicatrix / prevention & control
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Extracellular Matrix / drug effects
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Extracellular Matrix / ultrastructure
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Fibrillar Collagens / drug effects
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Fibrillar Collagens / ultrastructure
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Fibroblast Growth Factor 2 / antagonists & inhibitors
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Fibroblast Growth Factor 2 / pharmacology*
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Fibroblasts / drug effects*
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Fibroblasts / metabolism
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Humans
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Morpholines / pharmacology
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Myofibroblasts / drug effects*
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Myofibroblasts / metabolism
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Myosin Light Chains / drug effects
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Myosin Light Chains / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Pyridines / pharmacology
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Signal Transduction*
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Transforming Growth Factor beta1 / pharmacology*
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Wound Healing
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rac1 GTP-Binding Protein / metabolism
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rhoA GTP-Binding Protein / metabolism
Substances
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ACTA2 protein, human
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Actins
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Amides
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Chromones
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Fibrillar Collagens
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Morpholines
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Myosin Light Chains
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Phosphoinositide-3 Kinase Inhibitors
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Pyridines
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RAC1 protein, human
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Transforming Growth Factor beta1
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Fibroblast Growth Factor 2
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RHOA protein, human
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Y 27632
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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rac1 GTP-Binding Protein
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rhoA GTP-Binding Protein