Role of Nutrient-Sensing Signals in the Pathogenesis of Diabetic Nephropathy

Table 3

The activity and pathophysiological roles of Sirt1 in kidney disease.

Experimental type	Renal outcome/phenotype	Mechanism	Reference
Activity/expression
STZ-diabetic rats	Sirt1 expression↓	Unclear	Tikoo et al. [40]
STZ-diabetic rats	Sirt1 expression↓	Unclear	Li et al. [41]
Db/db mice	Sirt1 expression→	Unclear	Kitada et al. [35]
Calorie-restricted rats	Sirt1 expression↑	Insulin/IGF-1↓	Cohen et al. [42]
STZ- and db/db mice	Sirt1 expression↓	NMN depletion	Hasegawa et al. [43]
Pathophysiological roles
Sirt1^+/− mice (PTECs)	Renal aging↑	Autophagy deficiency	Kume et al. [16]
Sirt1^+/− mice (Medullary cells)	UUO-induced renal fibrosis↑	Decrease of Cox2 expression	He et al. [44]
PTECs-specific Sirt1-TG mice	ROS- and cisplatin-induced PTECs damage↓	Increase of catalase expression	Hasegawa et al. [45]
Treatment with resveratrol	UUO-induced fibrosis↓	Suppression of TGF𝛽-Smad3 pathway	Li et al. [46]
Sirt1 overexpression (mesangial cells)	ROS-induced apoptosis↓	Inactivation of p53	Kume et al. [47]
Sirt1 overexpression (mesangial cells)	TGF𝛽-induced apoptosis↓	Inactivation of Smad7	Kume et al. [48]
Treatment of SRT1720 (PTECs)	Mitochondrial biogenesis↑, ROS↓	Activation of PGC-1𝛼	Funk et al. [49]
PTECs-specific Sirt1-TG mice	Diabetes-induced podocyte injury↓	Epigenetic mechanism	Hasegawa et al. [43]

STZ; streptozotocin, PTECs: proximal tubular epithelial cells, ROS: reactive oxygen species, UUO: unilateral ureteral obstruction, TGF𝛽: transforming growth factor 𝛽, IGF-1: insulin-like growth factor 1, Cox2: cyclooxygenase 2, PGC-1𝛼: peroxisome proliferator-activated receptor 𝛾 coactivator-1𝛼, and NMN; nicotinamide mononucleotide.