Send to

Choose Destination
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

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.
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
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.
Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.
Xenotransplantation Program/Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, 35233, USA.


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.


endothelial cell; klotho; xenoreactive antibodies; xenotransplantation

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center