title: Fussel-15, a new player in wound healing, is deregulated in keloid and localized scleroderma.
abstract: Dermal wound healing depends on highly complex interplay among various cytokines and cell types. Disruption of this process can result in impaired healing in the form of excessive scarring, as is the case in fibrotic diseases such as keloid and scleroderma. In the present study, we found Fussel-15, a new member of the Ski/Sno family of TGF-β/BMP signaling repressors, to be expressed in early wound healing and constantly overexpressed in keloid-derived and scleroderma-derived fibroblasts. Comparing the results of three-dimensional free-floating and attached-released in vitro wound healing assays, we observed that Fussel-15 is expressed during the migratory phase in the free-floating assay, indicating that Fussel-15 might play a role during fibroblast migration. Fussel-15-transfected fibroblasts showed greater migration ability in a scratch wound healing assay, compared with control-transfected cells. This migratory phenotype due to Fussel-15 was confirmed by increased peripheral F-actin localization and modifications in size, amount, and distribution of focal adhesion complexes, which were observed using F-actin and focal adhesion kinase (FAK) immunofluorescence staining, respectively. The present results suggest that expression of Fussel-15 during wound healing might promote fibroblast migration. Permanent expression of Fussel-15 in keloid and skin sclerosis fibroblasts could be involved in the pathogenesis of these conditions, but the molecular mechanism underlying this up-regulation remains to be determined.
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Arndt
authors.forename: Johanna
authors.initials: J
authors.lastname: Schmidt
authors.forename: Eva
authors.initials: E
authors.lastname: Wacker
authors.forename: Sigrid
authors.initials: S
authors.lastname: Karrer
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D000199:Actins / Q000378:metabolism; D001681:Biological Assay; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056970:Co-Repressor Proteins; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D022001:Focal Adhesions / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007627:Keloid / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012594:Scleroderma, Localized / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000199:Actins; D056970:Co-Repressor Proteins; D012097:Repressor Proteins; C522810:SKOR1 protein, human; D016212:Transforming Growth Factor beta; D003094:Collagen