Klotho attenuated antibody‐mediated porcine endothelial cell activation and injury. (28th January 2017)

• Record Type: Journal Article
• Authors: Liu, Lu; Gao, Hanchao; Hong, Chungu; He, Chen; Pan, Dengke; Dai, Yifan; Hara, Hidetaka; Cooper, David K. C.; Li, Zesong; Cai, Zhiming; Mou, Lisha
• Is Part Of: Xenotransplantation. Volume 24:Number 1(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-01-28
• Subjects: endothelial cell -- klotho -- xenoreactive antibodies -- xenotransplantation; Xenografts -- Periodicals; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/xen.12286
• Languages: English
• ISSNs: 0908-665X

Abstract

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.