Sirtuin and metabolic kidney disease

Shu Wakino, Kazuhiro Hasegawa, Hiroshi Itoh

Research output: Contribution to journalReview articlepeer-review

100 Citations (Scopus)


Sirtuin is a nicotinamide adenine dinucleotide-dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti-fibrosis effects, anti-oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule-specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy.

Original languageEnglish
Pages (from-to)691-698
Number of pages8
JournalKidney international
Issue number4
Publication statusPublished - 2015 Oct 3


  • cell signaling
  • chronic kidney disease
  • diabetic nephropathy
  • mitochondria
  • podocyte
  • proximal tubule

ASJC Scopus subject areas

  • Nephrology


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