The effect of imatinib (Glivec) on scleroderma and normal dermal fibroblasts: a preclinical study.

نویسندگان

  • A Soria
  • M Cario-André
  • S Lepreux
  • H R Rezvani
  • J M Pasquet
  • C Pain
  • T Schaeverbeke
  • F X Mahon
  • A Taïeb
چکیده

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.

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عنوان ژورنال:
  • Dermatology

دوره 216 2  شماره 

صفحات  -

تاریخ انتشار 2008