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Platelet-Derived Growth Factor as a Therapeutic Target for Systemic Autoimmune Diseases

机译：血小板衍生的生长因子作为系统性自身免疫性疾病的治疗靶标

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Some systemic rheumatic diseases and disorders, especially fibrotic and vascular disorders, are often refractory to corticosteroid therapy. Recently, ever accumulating evidence suggests that platelet-derived growth factor (PDGF) is involved in those refractory diseases. Imatinib mesylate inhibits the activation of PDGF receptor as well as c-Abl, Bcr-Abl and c-Kit tyrosine kinases. It has therefore been widely used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Imatinib effectively suppresses the activation and proliferation of fibroblasts, mesangial cells and smooth muscle cells both in vitro and in vivo. Additionally, it has recently been reported that some patients with rheumatoid arthritis or idiopathic pulmonary arterial hypertension demonstrated a good clinical response to imatinib therapy. Imatinib may therefore overcome the limitations of current therapeutic strategy with corticosteroids and immunosuppressive agents for refractory diseases, such as systemic sclerosis and interstitial lung diseases, without clinical intolerability.
机译：一些系统性风湿病和疾病，尤其是纤维化和血管疾病，通常对皮质类固醇激素治疗无效。最近，越来越多的证据表明血小板源性生长因子（PDGF）参与了那些难治性疾病。甲磺酸伊马替尼抑制PDGF受体以及c-Abl，Bcr-Abl和c-Kit酪氨酸激酶的活化。因此，它已被广泛用于治疗慢性粒细胞白血病和胃肠道间质瘤。伊马替尼在体外和体内均能有效抑制成纤维细胞，肾小球膜细胞和平滑肌细胞的活化和增殖。另外，最近有报道说，一些类风湿性关节炎或特发性肺动脉高压患者表现出对伊马替尼治疗的良好临床反应。因此，伊马替尼可以克服皮质类固醇和免疫抑制剂目前治疗策略的局限性，而无临床耐受性，可用于难治性疾病，例如全身性硬化症和间质性肺病。

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