SIRT1 is a potential drug target for treatment of diabetic kidney disease

Yifei Zhong, Kyung Lee, John Cijiang He

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations

Abstract

Multiple studies have demonstrated a critical role of Sirtuin-1 (SIRT1) deacetylase in protecting kidney cells from cellular stresses. A protective role of SIRT1 has been reported in both podocytes and renal tubular cells in multiple kidney disease settings, including diabetic kidney disease (DKD). We and others have shown that SIRT1 exerts renoprotective effects in DKD in part through the deacetylation of transcription factors involved in the disease pathogenesis, such as p53, FOXO, RelA/p65NF-κB, STAT3, and PGC1α/PPARγ. Recently we showed that the podocyte-specific overexpression of SIRT1 attenuated proteinuria and kidney injury in an experimental model of DKD, further confirming SIRT1 as a potential target to treat kidney disease. Known agonists of SIRT1 such as resveratrol diminished diabetic kidney injury in several animal models. Similarly, we also showed that puerarin, a Chinese herbal medicine compound, activates SIRT1 to provide renoprotection in mouse models of DKD. However, as these are nonspecific SIRT1 agonists, we recently developed a more specific and potent SIRT1 agonist (BF175) that significantly attenuated diabetic kidney injury in type 1 diabetic OVE26 mice. We also previously reported that MS417, a bromodomain inhibitor that disrupts the interaction between the acetyl-residues of NF-κB and bromodomain-containing protein 4 (BRD4) also attenuates DKD. These results suggest that SIRT1 agonists and bromodomain inhibitors could be potential new therapuetic treatments against DKD progression.

Original languageEnglish
Article number624
JournalFrontiers in Endocrinology
Volume9
Issue numberOCT
DOIs
StatePublished - 17 Oct 2018

Keywords

  • Acetylation
  • Bromodomain inhibitor
  • Diabetic kidney disease
  • Podocytes
  • SIRT1

Fingerprint

Dive into the research topics of 'SIRT1 is a potential drug target for treatment of diabetic kidney disease'. Together they form a unique fingerprint.

Cite this