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Xenotransplantation. 2017 Jan;24(1). doi: 10.1111/xen.12286. Epub 2017 Jan 28.

Klotho attenuated antibody-mediated porcine endothelial cell activation and injury.

Author information

1
Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
2
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
3
Key Laboratory of Farm Animal Genetic Resource and Germplasm Innovation of Ministry of Agriculture, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Shenzhen, China.
4
Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
5
Xenotransplantation Program/Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, 35233, USA.

Abstract

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-1α. NF-κB activation, IκBα 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.

KEYWORDS:

endothelial cell; klotho; xenoreactive antibodies; xenotransplantation

PMID:
28130792
DOI:
10.1111/xen.12286
[Indexed for MEDLINE]

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