title: Small cytoskeleton-associated molecule, fibroblast growth factor receptor 1 oncogene partner 2/wound inducible transcript-3.0 (FGFR1OP2/wit3.0), facilitates fibroblast-driven wound closure.
abstract: Wounds created in the oral cavity heal rapidly and leave minimal scarring. We have examined a role of a previously isolated cDNA from oral wounds encoding wound inducible transcript-3.0 (wit3.0), also known as fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2). FGFR1OP2/wit3.0 was highly expressed in oral wound fibroblasts without noticeable up-regulation of alpha-smooth muscle actin. In silico analyses, denaturing and nondenaturing gel Western blot, and immunocytology together demonstrated that FGFR1OP2/wit3.0 were able to dimerize and oligomerize through coiled-coil structures and appeared to associate with cytoskeleton networks in oral wound fibroblasts. Overexpression of FGFR1OP2/wit3.0 increased the floating collagen gel contraction of naïve oral fibroblasts to the level of oral wound fibroblasts, which was in turn attenuated by small-interfering RNA knockdown. The FGFR1OP2/wit3.0 synthesis did not affect the expression of collagen I as well as procontractile peptides such as alpha-smooth muscle actin, and transforming growth factor-beta1 had no effect on FGFR1OP2/wit3.0 expression. Fibroblastic cells derived from embryonic stem cells carrying FGFR1OP2/wit3.0 (+/-) mutation showed significant retardation in cell migration. Thus, we postulate that FGFR1OP2/wit3.0 may regulate cell motility and stimulate wound closure. FGFR1OP2/wit3.0 was not up-regulated during skin wound healing; however, when treated with FGFR1OP2/wit3.0 -expression vector, the skin wound closure was significantly accelerated, resulting in the limited granulation tissue formation. Our data suggest that FGFR1OP2/wit3.0 may possess a therapeutic potential for wound management.
authors: The Weintraub Center for Reconstructive Biotechnology, University of California, Los Angeles, School of Dentistry, Los Angeles, CA 90095-1668, USA.
authors: Audrey
authors: A
authors: Lin
authors: Akishige
authors: A
authors: Hokugo
authors: Jae
authors: J
authors: Choi
authors: Ichiro
authors: I
authors: Nishimura
mesh_terms: D000818:Animals; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005782:Gels; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D003598:Cytoskeletal Proteins; C547759:FGFR1OP2 protein, mouse; D005782:Gels; D011506:Proteins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C460419:wit 3.0 protein, human; C480856:wound-inducible transcript 3.0, rat; D003094:Collagen; D018995:Myosin Heavy Chains