α-Klotho Expression in Human Tissues

作者：Kenneth Lim, Arnoud Groen, Guerman Molostvov, Tzongshi Lu, Kathryn S. Lilley, David Snead, Sean James, Ian B. Wilkinson, Stephen Ting, Li-Li Hsiao, Thomas F. Hiemstra, Daniel Zehnder · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2015 · DOI：10.1210/jc.2015-1800 · 被引用次数：211 · 研究领域：Parathyroid Disorders and Treatments、Blood properties and coagulation、Caveolin-1 and cellular processes

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 systemwide tissue expression of transmembrane α-Klotho in humans. We have employed next-generation targeted proteomic analysis using parallel reaction monitoring 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, whereas 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 parallel reaction monitoring mass spectrometry (data deposited at ProteomeXchange, PXD002775) identifying peptides specific for the full-length, transmembrane α-Klotho isoform. CONCLUSIONS: The data presented confirm α-Klotho expression in the kidney tubule and in the artery and provide evidence of α-Klotho expression across organ systems and cell types that has not previously been described in humans.