RRC ID 78188
Author Aihara S, Torisu K, Uchida Y, Imazu N, Nakano T, Kitazono T.
Title Spermidine from arginine metabolism activates Nrf2 and inhibits kidney fibrosis.
Journal Commun Biol
Abstract Kidney metabolism may be greatly altered in chronic kidney disease. Here we report that arginine metabolism is the most altered in unilateral ureteral obstruction (UUO)-induced fibrosis of the kidneys in metabolomic analysis. Spermidine is the most increased metabolite of arginine. In human glomerulonephritis, the amount of spermidine shown by immunostaining is associated with the amount of fibrosis. In human proximal tubule cells, spermidine induces nuclear factor erythroid 2-related factor 2 (Nrf2). Subsequently, fibrotic signals, such as transforming growth factor β1 secretion, collagen 1 mRNA, and oxidative stress, represented by a decrease in the mitochondrial membrane potential is suppressed by spermidine. UUO kidneys of Arg2 knockout mice show less spermidine and significantly exacerbated fibrosis compared with wild-type mice. Nrf2 activation is reduced in Arg2 knockout UUO kidneys. Spermidine treatment prevents significant fibrotic progression in Arg2 knockout mice. Spermidine is increased in kidney fibrosis, but further increases in spermidine may reduce fibrosis.
Volume 6(1)
Pages 676
Published 2023-6-28
DOI 10.1038/s42003-023-05057-w
PII 10.1038/s42003-023-05057-w
PMID 37380734
PMC PMC10307812
MeSH Animals Arginine Fibrosis Humans Kidney Mice Mice, Knockout NF-E2-Related Factor 2 / genetics Renal Insufficiency, Chronic* Spermidine / pharmacology Ureteral Obstruction* / complications
Human and Animal Cells Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711)