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Evidence that PI3K, Rac, Rho, and Rho kinase are involved in basic fibroblast growth factor‐stimulated fibroblast–Collagen matrix contraction
Author(s) -
Abe Masatoshi,
Sogabe Yoko,
Syuto Tomoko,
Yokoyama Yoko,
Ishikawa Osamu
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21359
Subject(s) - basic fibroblast growth factor , fibroblast , microbiology and biotechnology , rho kinase inhibitor , rho associated protein kinase , chemistry , focal adhesion , fibroblast growth factor , wound healing , signal transduction , growth factor , biology , immunology , biochemistry , receptor , in vitro
Abstract 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. Both bFGF and LPA promoted equally collagen matrix contraction well. Three different inhibitors, LY294002 for phosphatidylinositol‐3‐kinase (PI3K), C3 exotransferase for Rho and Y27632 for Rho kinase, suppressed the bFGF‐stimulated fibroblast–collagen matrix contraction. With bFGF stimulation, fibroblasts spread with prominent stress fiber network formation and focal adhesions. In the presence of Rho kinase inhibitor, focal adhesions and stress fibers were mostly lost. We demonstrated that bFGF stimulation for fibroblast caused transient Rac and Rho activation but did not activate Cdc42. In addition, bFGF enhanced fibroblast migration in wound healing assay. The present study implicates PI3K, Rac, Rho, and Rho kinase as being involved in bFGF‐stimulated collagen matrix contraction. The elucidation of bFGF‐triggered signal transduction may be an important clue to understand the roles of bFGF in wound healing. J. Cell. Biochem. 102: 1290–1299, 2007. © 2007 Wiley‐Liss, Inc.