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C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation

Hypertrophy is a prominent feature of damaged podocytes in diabetic kidney disease (DKD). mTORC1 hyperactivation leads to podocyte hypertrophy, but the detailed mechanism of how mTORC1 activation occurs under pathological conditions is not completely known. Moreover, reduced nephrin tyrosine phospho...

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Autores principales: Lee, Jiyoun, Koh, Ara, Jeong, Heeyoon, Kim, Eui, Ha, Tae-Sun, Saleem, Moin A., Ryu, Sung Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617844/
https://www.ncbi.nlm.nih.gov/pubmed/28955049
http://dx.doi.org/10.1038/s41598-017-12382-8
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author Lee, Jiyoun
Koh, Ara
Jeong, Heeyoon
Kim, Eui
Ha, Tae-Sun
Saleem, Moin A.
Ryu, Sung Ho
author_facet Lee, Jiyoun
Koh, Ara
Jeong, Heeyoon
Kim, Eui
Ha, Tae-Sun
Saleem, Moin A.
Ryu, Sung Ho
author_sort Lee, Jiyoun
collection PubMed
description Hypertrophy is a prominent feature of damaged podocytes in diabetic kidney disease (DKD). mTORC1 hyperactivation leads to podocyte hypertrophy, but the detailed mechanism of how mTORC1 activation occurs under pathological conditions is not completely known. Moreover, reduced nephrin tyrosine phosphorylation has been observed in podocytes under pathological conditions, but the molecular mechanism linking nephrin phosphorylation and pathology is unclear so far. In this study, we observed a significant increase in C1-Ten level in diabetic kidney and in high glucose-induced damaged podocytes. C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1. Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo. These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity. We suggest that C1-Ten contributes to the pathogenesis of DKD by inducing podocyte hypertrophy under high glucose conditions.
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spelling pubmed-56178442017-10-11 C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation Lee, Jiyoun Koh, Ara Jeong, Heeyoon Kim, Eui Ha, Tae-Sun Saleem, Moin A. Ryu, Sung Ho Sci Rep Article Hypertrophy is a prominent feature of damaged podocytes in diabetic kidney disease (DKD). mTORC1 hyperactivation leads to podocyte hypertrophy, but the detailed mechanism of how mTORC1 activation occurs under pathological conditions is not completely known. Moreover, reduced nephrin tyrosine phosphorylation has been observed in podocytes under pathological conditions, but the molecular mechanism linking nephrin phosphorylation and pathology is unclear so far. In this study, we observed a significant increase in C1-Ten level in diabetic kidney and in high glucose-induced damaged podocytes. C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1. Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo. These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity. We suggest that C1-Ten contributes to the pathogenesis of DKD by inducing podocyte hypertrophy under high glucose conditions. Nature Publishing Group UK 2017-09-27 /pmc/articles/PMC5617844/ /pubmed/28955049 http://dx.doi.org/10.1038/s41598-017-12382-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lee, Jiyoun
Koh, Ara
Jeong, Heeyoon
Kim, Eui
Ha, Tae-Sun
Saleem, Moin A.
Ryu, Sung Ho
C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation
title C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation
title_full C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation
title_fullStr C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation
title_full_unstemmed C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation
title_short C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation
title_sort c1-ten is a ptpase of nephrin, regulating podocyte hypertrophy through mtorc1 activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617844/
https://www.ncbi.nlm.nih.gov/pubmed/28955049
http://dx.doi.org/10.1038/s41598-017-12382-8
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