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PMID:19959814

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Citation

Lin, A, Hokugo, A, Choi, J and Nishimura, I (2010) 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. Am. J. Pathol. 176:108-21

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.

Links

PubMed PMC2797874 Online version:10.2353/ajpath.2010.090256

Keywords

Animals; Base Sequence; Cell Movement/drug effects; Collagen/metabolism; Cytoskeletal Proteins/genetics; Cytoskeletal Proteins/metabolism; Cytoskeleton/drug effects; Cytoskeleton/metabolism; Fibroblasts/drug effects; Fibroblasts/metabolism; Fibroblasts/pathology; Gels; Gene Knockdown Techniques; Humans; Mice; Molecular Sequence Data; Mouth Mucosa/drug effects; Mouth Mucosa/metabolism; Mouth Mucosa/pathology; Mutation/genetics; Myosin Heavy Chains/genetics; Myosin Heavy Chains/metabolism; Polymorphism, Single Nucleotide/genetics; Protein Transport/drug effects; Proteins/genetics; Proteins/metabolism; RNA, Small Interfering/metabolism; Rats; Transforming Growth Factor beta1/pharmacology; Wound Healing/drug effects

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:FGOP2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FGOP2

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9CRA9

F

Seeded From UniProt

complete

MOUSE:FGOP2

acts_upstream_of_or_within

GO:0042060: wound healing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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