Klotho attenuated antibody-mediated porcine endothelial cell activation and injury

文献类型: 外文期刊

第一作者: Liu, Lu

作者: Liu, Lu;Gao, Hanchao;Hong, Chungu;He, Chen;Li, Zesong;Cai, Zhiming;Mou, Lisha;Liu, Lu;Gao, Hanchao;Pan, Dengke;Dai, Yifan;Hara, Hidetaka;Cooper, David K. C.

作者机构:

关键词: endothelial cell;klotho;xenoreactive antibodies;xenotransplantation

期刊名称:XENOTRANSPLANTATION ( 影响因子:3.907; 五年影响因子:3.948 )

ISSN: 0908-665X

年卷期: 2017 年 24 卷 1 期

页码:

收录情况: SCI

摘要: Long-term success in pig-to-primate xenotransplantation is currently hampered by acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and injury. Klotho has anti-apoptotic, anti-inflammatory effects on EC and protects EC against reactive oxygen species, rendering klotho a promising molecule to control AVR. In this study, porcine ECs were pre-incubated with klotho and then exposed to xenoreactive antibodies and complement. Real-time PCR revealed that klotho suppressed antibody-induced pro-inflammatory gene expression of VCAM-1 and IL-1 alpha. NF-kappa(B) activation, I kappa B alpha phosphorylation, was also attenuated by klotho administration. Furthermore, klotho induced in porcine EC resistance against complement-dependent cytotoxicity. Accompanying this change, the binding of IgG and IgM xenoreactive antibodies to porcine EC was decreased and the expression of anti--inflammatory gene HO-1 was upregulated. These findings indicated that klotho protein protected porcine EC from activation and injury caused by binding of xenoreactive antibodies and was a promising candidate molecule in a multitransgenic pig strategy for xenotransplantation.

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