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J Clin Endocrinol Metab. 2015 Oct;100(10):E1308-18. doi: 10.1210/jc.2015-1800. Epub 2015 Aug 17.

α-Klotho Expression in Human Tissues.

Author information

1
Renal Division (K.L., T.L., L.-L.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Cambridge Centre for Proteomics (A.G., K.S.L., T.F.H.), and School of Clinical Medicine (I.B.W., T.F.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Department of Pathology (D.S., S.J., S.T.), University Hospitals Coventry and Warwickshire, NHS Trust, Coventry CV2 2DX, United Kingdom; and Division of Translational Research (G.M., D.Z.), Warwick Medical School, University of Warwick, Coventry CV2 2DX, United Kingdom.

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 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.

PMID:
26280509
PMCID:
PMC4596032
DOI:
10.1210/jc.2015-1800
[Indexed for MEDLINE]
Free PMC Article

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