Pre-emptive short-term nicotinamide mononucleotide treatment in a mouse model of diabetic nephropathy

Itaru Yasuda, Kazuhiro Hasegawa, Yusuke Sakamaki, Hirokazu Muraoka, Takahisa Kawaguchi, Ei Kusahana, Takashi Ono, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Background The activation of NAD1-dependent deacetylase, Sirt1, by the administration of nicotinamide mononucleotide (NMN) ameliorates various aging-related diseases. Methods Diabetic db/db mice were treated with NMN transiently for 2 weeks and observed for effects on diabetic nephropathy (DN). Results At 14 weeks after the treatment period, NMN attenuated the increases in urinary albumin excretion in db/db mice without ameliorating hemoglobin A1c levels. Short-term NMN treatment mitigated mesangium expansion and foot process effacement, while ameliorating decreased Sirt1 expression and increased claudin-1 expression in the kidneys of db/db mice. This treatment also improved the decrease in the expression of H3K9me2 and DNMT1. Short-term NMN treatment also increased kidney concentrations of NAD1 and the expression of Sirt1 and nicotinamide phosphoribosyltransferase (Nampt), and it maintained nicotinamide mononucleotide adenyltransferase1 (Nmnat1) expression in the kidneys. In addition, survival rates improved after NMN treatment. Conclusions: Short-term NMN treatment in early-stage DN has remote renal protective effects through the upregulation of Sirt1 and activation of the NAD1 salvage pathway, both of which indicate NMN legacy effects on DN.

本文言語English
ページ(範囲)1355-1370
ページ数16
ジャーナルJournal of the American Society of Nephrology
32
6
DOI
出版ステータスPublished - 2021 6
外部発表はい

ASJC Scopus subject areas

  • 腎臓病学

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