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A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma

αKlotho is primarily known to express as a transmembrane protein. Proteolytic cleavage results in shedding of the extracellular domain which enters systemic circulation. A truncated form of αKlotho resulting from alternative splicing of the αKLOTHO transcript exists and is believed to be secreted, t...

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Autores principales: Jadhav, Shreyas, Tripathi, Sudipta, Chandrekar, Anil, Waikar, Sushrut S., Hsiao, Li-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822350/
https://www.ncbi.nlm.nih.gov/pubmed/33481901
http://dx.doi.org/10.1371/journal.pone.0245614
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author Jadhav, Shreyas
Tripathi, Sudipta
Chandrekar, Anil
Waikar, Sushrut S.
Hsiao, Li-Li
author_facet Jadhav, Shreyas
Tripathi, Sudipta
Chandrekar, Anil
Waikar, Sushrut S.
Hsiao, Li-Li
author_sort Jadhav, Shreyas
collection PubMed
description αKlotho is primarily known to express as a transmembrane protein. Proteolytic cleavage results in shedding of the extracellular domain which enters systemic circulation. A truncated form of αKlotho resulting from alternative splicing of the αKLOTHO transcript exists and is believed to be secreted, thereby also entering systemic circulation. Existing ELISA methods fail to distinguish between the two circulating isoforms resulting in inconsistencies in assessing circulating αKlotho levels. We have exploited a unique 15aa peptide sequence present in the alternatively spliced secreted isoform to generate an antibody and show that it is able to specifically detect only the secreted Klotho isoform in human plasma. This finding will facilitate in distinguishing the levels of different circulating Klotho isoforms in health and disease and enhance their potential to serve as a biomarker for CKD and other conditions.
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spelling pubmed-78223502021-01-29 A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma Jadhav, Shreyas Tripathi, Sudipta Chandrekar, Anil Waikar, Sushrut S. Hsiao, Li-Li PLoS One Research Article αKlotho is primarily known to express as a transmembrane protein. Proteolytic cleavage results in shedding of the extracellular domain which enters systemic circulation. A truncated form of αKlotho resulting from alternative splicing of the αKLOTHO transcript exists and is believed to be secreted, thereby also entering systemic circulation. Existing ELISA methods fail to distinguish between the two circulating isoforms resulting in inconsistencies in assessing circulating αKlotho levels. We have exploited a unique 15aa peptide sequence present in the alternatively spliced secreted isoform to generate an antibody and show that it is able to specifically detect only the secreted Klotho isoform in human plasma. This finding will facilitate in distinguishing the levels of different circulating Klotho isoforms in health and disease and enhance their potential to serve as a biomarker for CKD and other conditions. Public Library of Science 2021-01-22 /pmc/articles/PMC7822350/ /pubmed/33481901 http://dx.doi.org/10.1371/journal.pone.0245614 Text en © 2021 Jadhav et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jadhav, Shreyas
Tripathi, Sudipta
Chandrekar, Anil
Waikar, Sushrut S.
Hsiao, Li-Li
A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
title A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
title_full A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
title_fullStr A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
title_full_unstemmed A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
title_short A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
title_sort novel antibody for the detection of alternatively spliced secreted klotho isoform in human plasma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822350/
https://www.ncbi.nlm.nih.gov/pubmed/33481901
http://dx.doi.org/10.1371/journal.pone.0245614
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