title: Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression.
abstract: Although hypertrophic scars (HTSs) and keloids are challenging problems, their pathogenesis is not well understood, making therapy difficult. We showed that matrix metalloproteinase (MMP)-1 expression was downregulated in HTS compared with normal skin from the same patients, whereas type 1 and 3 collagen and transforming growth factor-β (TGF-β) were upregulated. These differences, however, were not seen in cultured fibroblasts, suggesting the involvement of microenvironmental factors in the pathogenesis of HTS. Fibroblast growth factor-2 (FGF-2) highly upregulated the expression of MMP-1 and hepatocyte growth factor (HGF) in both HTS-derived and control fibroblasts; the upregulation was reversed by extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors. An animal study using human HTS tissue implanted into nude mice indicated that controlled-release FGF-2 resulted in significantly less weight and decreased hydroxyproline content in HTS. Degradation of collagen fibers in FGF-2-treated HTS was also confirmed histologically. Western blotting showed that FGF-2-treated HTS expressed significantly higher MMP-1 protein than control. Decreased MMP-1 expression may be an important transcriptional change in HTS, and its reversal as well as upregulation of HGF by FGF-2 could be a new therapeutic approach for HTS.
authors.affiliation: Department of Plastic Surgery, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Eto
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Suga
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Aoi
authors.forename: Harunosuke
authors.initials: H
authors.lastname: Kato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Doi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kuno
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yoshimura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy*; D017931:DNA Primers; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000627:therapeutic use*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D020781:Matrix Metalloproteinase 1