Role of sirtuin-1 in diabetic nephropathy

Diabetic nephropathy (DN) is a research priority for scientists around the world because of its high prevalence and poor prognosis. Although several mechanisms have been shown to be involved in its pathogenesis and many useful drugs have been developed, the management of DN remains challenging. Incr...

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Bibliographic Details
Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2019-03, Vol.97 (3), p.291-309
Main Authors: Wang, Wanning, Sun, Weixia, Cheng, Yanli, Xu, Zhonggao, Cai, Lu
Format: Article
Language:English
Subjects:
Adenine
Advanced glycosylation end products
Apoptosis
Autophagy
Biomedical and Life Sciences
Biomedicine
Deacetylation
Diabetes
Diabetes mellitus
Diabetic nephropathy
Forkhead protein
Glycosylation
Histones
Homeostasis
Homology
Human Genetics
Hypoxia
Hypoxia-inducible factors
Internal Medicine
Mesangial cells
miRNA
Molecular Medicine
NAD
NADPH
Nephropathy
Nicotinamide
Nicotinamide adenine dinucleotide
Oxidative stress
p53 Protein
Pathogenesis
Phagocytosis
Review
Transcription factors
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Summary:Diabetic nephropathy (DN) is a research priority for scientists around the world because of its high prevalence and poor prognosis. Although several mechanisms have been shown to be involved in its pathogenesis and many useful drugs have been developed, the management of DN remains challenging. Increasing amounts of evidence show that silent information regulator 2 homolog 1 (sirtuin-1), a nicotinamide adenine dinucleotide (NAD+)–dependent protein deacetylase, plays a crucial role in the pathogenesis and development of DN. Clinical data show that gene polymorphisms of sirtuin-1 affect patient vulnerability to DN. In addition, upregulation of sirtuin-1 attenuates DN in various experimental models of diabetes and in renal cells, including podocytes, mesangial cells, and renal proximal tubular cells, incubated with high concentrations of glucose or advanced glycation end products. Mechanistically, sirtuin-1 has its renoprotective effects by modulating metabolic homeostasis and autophagy, resisting apoptosis and oxidative stress, and inhibiting inflammation through deacetylation of histones and the transcription factors p53, forkhead box group O, nuclear factor-κB, hypoxia-inducible factor-1α, and others. Furthermore, some microRNAs have been implicated in the progression of DN because they target sirtuin-1 mRNA. Several synthetic drugs and natural compounds have been identified that upregulate the expression and activity of sirtuin-1, which protects against DN. The present review will summarize advances in knowledge regarding the role of sirtuin-1 in the pathogenesis of DN. The available evidence implies that sirtuin-1 has great potential as a clinical target for the prevention and treatment of diabetes.
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-019-01743-7