期刊
DERMATOLOGY
卷 216, 期 2, 页码 109-117出版社
KARGER
DOI: 10.1159/000111507
关键词
imatinib; scleroderma; normal dermal fibroblasts
类别
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 ad-nexae 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. Copyright (c) 2008 S. Karger AG, Basel
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