α-klotho expression in human tissues

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

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 confirmα-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.

Original languageEnglish
Pages (from-to)E1308-E1318
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number10
DOIs
Publication statusPublished - 1 Oct 2015
Externally publishedYes

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