α-Klotho expressison in human tissue
Journal of Clinical Endocrinology & Metabolism
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Lim, K., Groen, A., Molostvov, G., Lu, T., Lilley, K., Snead, D., James, S., et al. (2015). α-Klotho expressison in human tissue. Journal of Clinical Endocrinology & Metabolism, 100 E1308-E1318. https://doi.org/10.1210/jc.2015-1800
Context: α-Klotho has emerged as a powerful regulator of the aging process. To-date, the expression profile of α-Klotho in human tissues is unknown and its existence in some human tissue types is subject to much controversy. Objective: This is the first study to characterize system-wide tissue expression of transmembrane α-Klotho in humans. We have employed next generation targeted proteomic analysis using Parallel Reaction Monitoring (PRM) in parallel with conventional antibody-based methods to determine the expression and spatial distribution of human α-Klotho expression in health. Results: The distribution of α-Klotho in human tissues from various organ systems, including arterial, epithelial, endocrine, reproductive and neuronal tissues was first identified by immunohistochemistry. Kidney tissues showed strong α-Klotho expression, while liver did not reveal a detectable signal. These results were next confirmed by western blotting of both whole tissues and primary cells. To validate our antibody-based results, α-Klotho expressing tissues were subjected to PRM mass spectrometry identifying peptides specific for the full length, transmembrane α-Klotho isoform. Conclusions: The data presented confirms α-Klotho expression in the kidney tubule and in artery, and provides evidence of α-Klotho expression across organ systems and cell-types that have not previously been described in humans.
Klotho, Proteomics, Extrarenal
K.L. received a Genzyme-Sanofi Fellowship in Nephrology grant. T.F.H. is funded by the NIHR award to the Cambridge Biomedical Research Centre and by NIHR grant 14/49/147. The Cambridge Aorta Study is funded by the British Heart Foundation.
British Heart Foundation (FS/12/8/29377)
External DOI: https://doi.org/10.1210/jc.2015-1800
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250359