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Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2

The activation of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, Sirt1, after the administration of nicotinamide mononucleotide (NMN) suppresses many diseases. However, the role of NMN and Sirt1 in focal glomerulosclerosis (FSGS) has not yet been elucidated. This study aimed to as...

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Autores principales: Hasegawa, Kazuhiro, Sakamaki, Yusuke, Tamaki, Masanori, Wakino, Shu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374671/
https://www.ncbi.nlm.nih.gov/pubmed/35962139
http://dx.doi.org/10.1038/s41598-022-18147-2
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author Hasegawa, Kazuhiro
Sakamaki, Yusuke
Tamaki, Masanori
Wakino, Shu
author_facet Hasegawa, Kazuhiro
Sakamaki, Yusuke
Tamaki, Masanori
Wakino, Shu
author_sort Hasegawa, Kazuhiro
collection PubMed
description The activation of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, Sirt1, after the administration of nicotinamide mononucleotide (NMN) suppresses many diseases. However, the role of NMN and Sirt1 in focal glomerulosclerosis (FSGS) has not yet been elucidated. This study aimed to assess the protective effect of NMN treatment in mice with adriamycin (ADR)-induced FSGS. Transient short-term NMN treatment was administered to 8-week-old ADR- or saline-treated BALB/c mice (Cont group) for 14 consecutive days. NMN alleviated the increase in urinary albumin excretion in the ADR-treated mice. NMN treatment mitigated glomerulosclerosis and ameliorated the reduced Sirt1 expression and elevated Claudin-1 expression in the kidneys of the mice. Moreover, this treatment improved the decrease in histone methylation and the expression level of Dnmt1 and increased the concentration of NAD(+) in the kidney. Dnmt1 epigenetically suppressed the expression of the NMN-consuming enzyme nicotinamide mononucleotide adenyltransferase1 (Nmnat1) by methylating the E-box in the promoter region and repressing the NAD-consuming enzyme PARP1. Additionally, NMN downregulated the expression of Nmnat1 in the ADR-treated mice. Short-term NMN treatment in FSGS has epigenetic renal protective effects through the upregulation of Sirt1 and suppression of the NAD and NMN consumers. The present study presents a novel treatment paradigm for FSGS.
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spelling pubmed-93746712022-08-14 Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2 Hasegawa, Kazuhiro Sakamaki, Yusuke Tamaki, Masanori Wakino, Shu Sci Rep Article The activation of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, Sirt1, after the administration of nicotinamide mononucleotide (NMN) suppresses many diseases. However, the role of NMN and Sirt1 in focal glomerulosclerosis (FSGS) has not yet been elucidated. This study aimed to assess the protective effect of NMN treatment in mice with adriamycin (ADR)-induced FSGS. Transient short-term NMN treatment was administered to 8-week-old ADR- or saline-treated BALB/c mice (Cont group) for 14 consecutive days. NMN alleviated the increase in urinary albumin excretion in the ADR-treated mice. NMN treatment mitigated glomerulosclerosis and ameliorated the reduced Sirt1 expression and elevated Claudin-1 expression in the kidneys of the mice. Moreover, this treatment improved the decrease in histone methylation and the expression level of Dnmt1 and increased the concentration of NAD(+) in the kidney. Dnmt1 epigenetically suppressed the expression of the NMN-consuming enzyme nicotinamide mononucleotide adenyltransferase1 (Nmnat1) by methylating the E-box in the promoter region and repressing the NAD-consuming enzyme PARP1. Additionally, NMN downregulated the expression of Nmnat1 in the ADR-treated mice. Short-term NMN treatment in FSGS has epigenetic renal protective effects through the upregulation of Sirt1 and suppression of the NAD and NMN consumers. The present study presents a novel treatment paradigm for FSGS. Nature Publishing Group UK 2022-08-12 /pmc/articles/PMC9374671/ /pubmed/35962139 http://dx.doi.org/10.1038/s41598-022-18147-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hasegawa, Kazuhiro
Sakamaki, Yusuke
Tamaki, Masanori
Wakino, Shu
Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2
title Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2
title_full Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2
title_fullStr Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2
title_full_unstemmed Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2
title_short Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2
title_sort nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the nmn/nad consumers mediated by twist2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374671/
https://www.ncbi.nlm.nih.gov/pubmed/35962139
http://dx.doi.org/10.1038/s41598-022-18147-2
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