Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1–SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.
Keywords: aging, diabetic nephropathy, sirtuin, SIRT1 (sirtuin 1)
Abbreviations: AGE, advanced glycation end-product; AMPK, AMP-activated protein kinase; AngII, angiotensin II; AT1R, angiotensin type 1 receptor; Atg, autophagy-related gene; BMAL1, brain and muscle ARNT (aryl hydrocarbon receptor nuclear translocator)-like 1; Bnip3, BCL2/adenovirus E1V 19-kDa interacting protein 3; CKD, chronic kidney disease; CR, calorie restriction; CRP, C-reactive protein; COX2, cyclo-oxygenase 2; α-ENaC, epithelial Na+ channel α-subunit; eNOS, endothelial NO synthase; ER, endoplasmic reticulum; FOXO, forkhead box O; FXR, farnesoid X receptor; H3K9, histone H3 Lys9; H3K9me3, H3K9 trimethylation; HIF, hypoxia-inducible factor; ICAM-1, intercellular adhesion molecule 1; Idh2, isocitrate dehydrogenase 2; IGF, insulin-like growth factor; IRS, insulin receptor substrate; LC3, light chain 3; LXR, liver X receptor; MCP-1, monocyte chemotactic protein-1; Mn-SOD, manganese superoxide dismutase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-κB; PARP, poly(ADP-ribose) polymerase; PER2, Period 2; PGC-1α, PPAR-γ co-activator-1α; PKC, protein kinase C; PPAR, peroxisome-proliferator-activated receptor; PTP1B, protein tyrosine phosphatase 1B; RAS, renin–angiotensin system; ROS, reactive oxygen species; Sir2, silent information regulator 2; SIRT1 etc., sirtuin 1 etc., SNP, single nucleotide polymorphism; SREBP, sterol-regulatory-element-binding protein; TGF, transforming growth factor; TNF-α, tumour necrosis factor α; UUO, unilateral ureteral obstruction; VCAM-1, vascular cell adhesion protein 1; WFR, Wistar fatty diabetic rat