Cutting Edge: Calcium/Calmodulin-Dependent Protein Kinase Type IV Is Essential for Mesangial Cell Proliferation and Lupus Nephritis
Cutting Edge: Calcium/Calmodulin-Dependent Protein Kinase Type IV Is Essential for Mesangial Cell Proliferation and Lupus Nephritis
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DOI：
10.4049/jimmunol.1102357
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发表时间：
2011-12-01
影响因子：
4.4
通讯作者：
Tsokos, George C.
中科院分区：
文献类型：
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作者：
Ichinose, Kunihiro;Rauen, Thomas;Tsokos, George C.
系统性红斑狼疮的肾脏受累仍然是发病率和死亡率的主要原因。虽然免疫参数，煽动肾损伤的特点，他们的联系，执行组织损伤的局部过程，是知之甚少。使用基因缺失和药理学抑制方法，我们证明了钙/钙调素依赖性蛋白激酶IV型，这有助于改变系统性红斑狼疮患者细胞因子的产生，控制自发和血小板源性生长因子刺激的系膜细胞增殖，并通过AP-1促进IL-6的产生。我们的研究确定了钙/钙调蛋白依赖性蛋白激酶IV型作为狼疮性肾炎的一个有价值的治疗靶点，并指出了局部肾脏因子在组织损伤表达中的重要性，如果靶向得当，应能增强临床获益并限制毒性。免疫学杂志，2011，187：5500-5504。
Renal involvement in systemic lupus erythematosus remains a major cause of morbidity and mortality. Although immune parameters that instigate renal damage have been characterized, their link to local processes, which execute tissue damage, is poorly understood. Using genetic-deletion and pharmacological-inhibition approaches, we demonstrated that calcium/calmodulin-dependent protein kinase type IV, which contributes to altered cytokine production in systemic lupus erythematosus patients, controls spontaneous and platelet-derived growth factor-stimulated mesangial cell proliferation and promotes IL-6 production through AP-1. Our studies identified calcium/calmodulin-dependent protein kinase type IV as a valuable treatment target for lupus nephritis and point out the importance of local kidney factors in the expression of tissue damage that, if properly targeted, should enhance clinical benefit and limit toxicity. The Journal of Immunology, 2011, 187: 5500-5504.