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Klotho attenuated antibody‐mediated porcine endothelial cell activation and injury
Author(s) -
Liu Lu,
Gao Hanchao,
Hong Chungu,
He Chen,
Pan Dengke,
Dai Yifan,
Hara Hidetaka,
Cooper David K. C.,
Li Zesong,
Cai Zhiming,
Mou Lisha
Publication year - 2017
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12286
Subject(s) - xenotransplantation , klotho , complement system , antibody , downregulation and upregulation , chemistry , microbiology and biotechnology , immunology , biology , transplantation , medicine , gene , biochemistry , kidney , endocrinology
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 EC s 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.