title: Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor beta--simultaneous application with basic fibroblast growth factor causes persistent fibrosis.
abstract: To establish an appropriate animal model of skin fibrosis by exogenous application of growth factors, we investigated the in vivo effects of transforming growth factor-beta by injection into subcutaneous tissue of newborn mice. Histological examination revealed that TGF-beta1, beta2, and beta3 induced granulation tissue formation after 3 days of injection, while these changes had disappeared after 7 days. The changes after 3 days of injection were more pronounced in the tissue injected with TGF-beta2 or beta3 than that with TGF-beta1. In situ hybridization analysis indicated that connective tissue growth factor mRNA was strongly expressed in the fibroblasts at the site of TGF-beta injection, which suggested that fibroblasts were activated by TGF-beta. Next, we investigated the cooperative effects of TGF-beta and other growth factors including basic fibroblast growth factor (bFGF). The simultaneous application of TGF-beta and bFGF caused apparent tissue fibrosis which persisted for at least 2 weeks, while bFGF alone caused slight fibrotic changes after 7 days of injection. Thus, we succeeded in establishing an animal model of skin fibrotic disorders by the exogenous addition of growth factors, and this animal will be useful for future studies in this area.
authors.affiliation: Department of Dermatology, Kanazawa University School of Medicine, Ishikawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shinozaki
authors.forename: S
authors.initials: S
authors.lastname: Kawara
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Kakinuma
authors.forename: A
authors.initials: A
authors.lastname: Igarashi
authors.forename: K
authors.initials: K
authors.lastname: Takehara
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D055513:Connective Tissue Growth Factor; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006099:Granuloma; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007279:Injections, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D055513:Connective Tissue Growth Factor