Imatinib Suppresses Cryoglobulinemia and Secondary Membranoproliferative Glomerulonephritis
Imatinib Suppresses Cryoglobulinemia and Secondary Membranoproliferative Glomerulonephritis
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DOI：
10.1681/asn.2008010036
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发表时间：
2009-01-01
影响因子：
13.6
通讯作者：
Alpers, Charles E.
中科院分区：
文献类型：
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作者：
Iyoda, Masayuki;Hudkins, Kelly L.;Alpers, Charles E.
伊马替尼是一种受体酪氨酸激酶抑制剂，可阻断c-Abl、c-Kit和PDGF受体的活性。我们测试了伊马替尼在胸腺基质淋巴细胞生成素转基因小鼠中的保护作用，这是一种cryopulinemia和相关膜增生性肾小球肾炎（MPGN）的模型，其中一些肾小球表现可能是由PDGF受体激活引起的。令人惊讶的是，在断奶时开始给予伊马替尼抑制了cryocellulin的产生，减轻了cryocellulinemia的肾损伤和全身特征。流式细胞术表明，骨髓中B细胞发育的抑制可能导致cryopulin产生的减少。此外，伊马替尼给药胸腺基质淋巴细胞生成素转基因小鼠与建立MPGN也减少cryopulin的生产和逆转肾脏和全身病变。这些数据表明，伊马替尼治疗可能是一种新的治疗方法，在人类的冷球蛋白血症和MPGN。
Imatinib is a receptor tyrosine kinase inhibitor that blocks the activity of c-Abl, c-Kit, and PDGF receptors. We tested the protective effects of imatinib in thymic stromal lymphopoietin transgenic mice, a model of cryoglobulinemia and associated membranoproliferative glomerulonephritis (MPGN), in which some glomerular manifestations likely result from PDGF receptor activation. Surprising, administration of imatinib beginning at weaning suppressed production of cryoglobulin, attenuating both the renal injury and systemic features of cryoglobulinemia. Flow cytometry suggested that inhibition of B cell development in the bone marrow likely caused the reduction in cryoglobulin production. In addition, administration of imatinib to thymic stromal lymphopoietin transgenic mice with established MPGN also diminished cryoglobulin production and reversed the renal and systemic lesions. These data suggest that treatment with imatinib may be a novel therapeutic approach for cryoglobulinemia and MPGN in humans.