BACKGROUND: Scleroderma skin overexpresses the platelet-derived growth factor receptor beta-subunit (PDGFR-beta) in dermal vessels and PDGFR-beta messenger RNA in cultured fibroblasts. Moreover, increased levels of PDGF and stimulatory autoantibodies to PDGFR have been identified in the serum of scleroderma patients. OBJECTIVE: Imatinib being an inhibitor of tyrosine kinase receptors such as PDGFR, its effect on scleroderma fibroblasts was evaluated in vitro as a preclinical therapeutic step. METHODS: The effect of imatinib on fibroblasts grown from normal or involved/uninvolved scleroderma skin was studied by Western blot and the methyltetrazolium test. The pattern of distribution of PDGFR-beta in scleroderma versus normal skin was studied by immunohistochemistry. RESULTS: In vitro, imatinib inhibited the proliferation of normal dermal and scleroderma fibroblasts at least partly via the inhibition of the phosphorylation of PDGFR. PDGFR-beta was expressed in the epidermis and adnexae in 5 lesional scleroderma biopsies and not in controls. CONCLUSION: This study suggests that imatinib can serve as therapy to limit dermal fibroblast proliferation in scleroderma. (c) 2008 S. Karger AG, Basel.
BACKGROUND:Scleroderma skin overexpresses the platelet-derived growth factor receptor beta-subunit (PDGFR-beta) in dermal vessels and PDGFR-beta messenger RNA in cultured fibroblasts. Moreover, increased levels of PDGF and stimulatory autoantibodies to PDGFR have been identified in the serum of sclerodermapatients. OBJECTIVE:Imatinib being an inhibitor of tyrosine kinase receptors such as PDGFR, its effect on scleroderma fibroblasts was evaluated in vitro as a preclinical therapeutic step. METHODS: The effect of imatinib on fibroblasts grown from normal or involved/uninvolved scleroderma skin was studied by Western blot and the methyltetrazolium test. The pattern of distribution of PDGFR-beta in scleroderma versus normal skin was studied by immunohistochemistry. RESULTS: In vitro, imatinib inhibited the proliferation of normal dermal and scleroderma fibroblasts at least partly via the inhibition of the phosphorylation of PDGFR. PDGFR-beta was expressed in the epidermis and adnexae in 5 lesional scleroderma biopsies and not in controls. CONCLUSION: This study suggests that imatinib can serve as therapy to limit dermal fibroblast proliferation in scleroderma. (c) 2008 S. Karger AG, Basel.
Authors: Vasiliki Kalliopi K Bournia; Panayiotis G Vlachoyiannopoulos; Carlo Selmi; Haralampos M Moutsopoulos; M Eric Gershwin Journal: Clin Rev Allergy Immunol Date: 2009-06 Impact factor: 8.667
Authors: George L Chen; Sally Arai; Mary E D Flowers; Joanne M Otani; Jingxin Qiu; Ethan C Cheng; Alex McMillan; Laura J Johnston; Judith A Shizuru; David B Miklos Journal: Blood Date: 2011-08-09 Impact factor: 22.113
Authors: Lorinda Chung; David F Fiorentino; Maya J Benbarak; Adam S Adler; Melissa M Mariano; Ricardo T Paniagua; Ausra Milano; M Kari Connolly; Boris D Ratiner; Robert L Wiskocil; Michael L Whitfield; Howard Y Chang; William H Robinson Journal: Arthritis Rheum Date: 2009-02