TARGETING TARGETED TREATMENT FOR IMMUNE AND NON-IMMUNE KIDNEY DISEASES.
TARGETING TARGETED TREATMENT FOR IMMUNE AND NON-IMMUNE KIDNEY DISEASES.
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发表时间：
2019
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通讯作者：
G. Tsokos;M. Tsokos
中科院分区：
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作者：
G. Tsokos;M. Tsokos
我们发现，在系统性红斑狼疮患者的T细胞、足细胞和系膜细胞中，以及在狼疮易感小鼠、局灶性节段性肾小球硬化患者的足细胞中，以及注射阿霉素的小鼠中，钙钙调素激酶IV都增加了。我们发现这是T细胞功能异常和肾小球损伤的原因。使用纳米颗粒(NLG)，装载了一种钙调素蛋白激酶IV的小型药物抑制剂，并用针对CD4的抗体标记，我们已经能够显示出对自身免疫和狼疮性肾炎的抑制。此外，使用标记了neparin抗体的NLG，我们显示了对狼疮易发小鼠的肾炎和暴露于阿霉素的小鼠肾小球损伤的抑制。我们建议开发以有针对性和精确度的方式向细胞输送药物的方法。
We have found that calcium calmodulin kinase IV is increased in T cells, podocytes, and mesangial cells from patients with systemic lupus erythematosus, as well as in lupus-prone mice, podocytes of patients with focal segmental glomerulosclerosis, and in mice injected with doxorubicin. We showed that this accounts for aberrant T cell function and glomerular damage. Using nanoparticles (nlg) loaded with a small drug inhibitor of calcium calmodulin kinase IV and tagged with antibodies directed to CD4 we have been able to show inhibition of autoimmunity and lupus nephritis. Also, using nlg tagged with antibodies to nephrin, we showed suppression of nephritis in lupus-prone mice and of glomerular damage in mice exposed to doxorubicin. We propose the development of approaches to deliver drugs to cells in a targeted and precise manner.