Analysis of Intracellular Signal Transduction of Basic Fibroblast Growth Factor-stimulated Fibroblast-collagen Matrix Contraction

概要

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Fibroblast-collagen matrix contraction has been used as a model system to study how cells organize connective tissue. Previous work showed that lysophosphatidic acid(LPA)-stimulated floating collagen matrix contraction is independent of Rho kinase while platelet-derived growth factor(PDGF)-stimulated contraction is Rho kinase-dependent. The current studies were carried out to determine the signaling mechanisms of basic fibroblast growth factor(bFGF)-stimulated fibroblast-collagen matrix contraction. LPA, PDGF and bFGF each equally well stimulated collagen matrix contraction. Both of two kinase inhibitors, LY294002 for phosphatidylinositol-3-Kinase(PI3K)and Y27632 for Rho kinase, suppressed the bFGF-stimulated fibroblast-collagen matrix contraction. With bFGF stimulation, fibroblasts in collagen matrix spread with prominent stress fiber network formation. The present study implicates PI3K→Rac→Rho→Rho kinase as being involved in bFGF-stimulated collagen matrix contraction. Since this pathway is similar to PDGF but not LPA, the combination therapy with bFGF and LPA is worthwhile to future strategy for the treatment of chronic cutaneous wound. The elucidation of bFGF-triggered signal transduction may be an important clue to understand the roles of bFGF and study the possibility of the combination therapy in wound healing.
日本皮膚科学会大阪地方会・日本皮膚科学会京滋地方会の論文