ID | 119528 |
Author |
Hasegawa, Kazuhiro
Tokushima University
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Shibata, Eriko
Tokushima University
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Inagaki, Taizo
Tokushima University
Minato, Masanori
Tokushima University
Yamaguchi, Sumiyo
Tokushima University
Shimizu, Ikuko
Tokushima University
Miyakami, Shinji
Tokushima University
Tada, Miho
Tokushima University
Wakino, Shu
Tokushima University
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Keywords | Sirtuin 1
Nicotinamide mononucleotide
Claudin-1
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Content Type |
Journal Article
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Description | The time for diabetic nephropathy (DN) to progress from mild to severe is long. Thus, methods to continuously repress DN are required to exert long-lasting effects mediated through epigenetic regulation. In this study, we demonstrated the ability of nicotinamide adenine dinucleotide (NAD) and its metabolites to reduce albuminuria through Sirt1- or Nampt-dependent epigenetic regulation. We previously reported that proximal tubular Sirt1 was lowered before glomerular Sirt1. Repressed glomerular Sirt1 was found to epigenetically elevate Claudin-1. In addition, we reported that proximal tubular Nampt deficiency epigenetically augmented TIMP-1 levels in Sirt6-mediated pathways, leading to type-IV collagen deposition and diabetic fibrosis. Altogether, we propose that the Sirt1/Claudin-1 axis may be crucial in the onset of albuminuria at the early stages of DN and that the Nampt/Sirt6/TIMP-1 axis promotes diabetic fibrosis in the middle to late stages of DN. Finally, administration of NMN, an NAD precursor, epigenetically potentiates the regression of the onset of DN to maintain Sirt1 and repress Claudin-1 in podocytes, suggesting the potential use of NAD metabolites as epigenetic medications for DN.
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Journal Title |
Clinical and Experimental Nephrology
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ISSN | 13421751
14377799
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NCID | AA11126935
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Publisher | Japanese Society of Nephrology|Springer
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Volume | 28
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Issue | 7
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Start Page | 599
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End Page | 607
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Published Date | 2024-04-08
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Rights | 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
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language |
eng
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Publisher
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departments |
Medical Sciences
University Hospital
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