SS-31, a Mitochondria-Targeting Peptide, Ameliorates Kidney Disease

Table 1

In vivo study of SS-31 in kidney disease.

Disease models	Renal protective effect	Cytokines	Renal function	Renal pathology	References
IR-induced AKI in rat	Mitochondrial protection, anti-inflammatory, antioxidative	↑GSH; ↓MDA, HO-1, MPO	↓Scr, BUN	↓Tubular necrosis, tubular cell detachment	[14]
IR-induced AKI in rat	Mitochondrial protection, antifibrotic, anti-inflammatory	↓TNF-α, CD68^+macrophages, CD3^+ lymphocytes, TGF-β, α-SMA	↓Scr, BUN	↓Endothelial cell injury, renal microvascular rarefaction	[55]
IR-induced AKI in rat	Mitochondrial protection, anti-inflammatory	↓TNF-α, IL-18, IL-1β	NA	↓Tubulointerstitial fibrosis, glomerulosclerosis, podocyte swelling	[48]
Contrast-induced AKI in rat	Antioxidative	↓MDA, NADPH, Nox4; ↑SOD, ATPase	↓Scr, FeNa%, FeK% ↑Ccr	↓Vacuolar degeneration, tubular dilation, protein cast, epithelial cell shedding	[38]
Contrast-induced AKI in mice	Antioxidative, antiapoptotic	↓NLRP 3, IL-1β, caspase 1, ROS, MDA	↓Scr, BUN	↓Tubular necrosis, tubulointerstitial lesions	[37]
Sepsis-induced AKI in	Mitochondrial protection, antioxidative, antiapoptotic, anti-inflammatory	↓TNF-α, MDA, NF-κB, iNOS, ROS, MPO	↓Scr, BUN	↓Kidney injury scores	[56, 57]
Renal artery stenosis in swine	Mitochondrial protection, antioxidative, antiapoptotic, anti-inflammatory	↓Caspase 3, Bcl-2 associated X-protein, PGC1α, PPAR-α, TNF-α, MCP-1, collagen IV↑VEGF	↑GFR	↓Tubular injury score, tubulointerstitial fibrosis, glomerular score ↑microvascular density	[36]
Renal artery stenosis in pig	Mitochondrial protection, antifibrotic	↓Superoxide anion; ↑Cardiolipin, COX-4	↑GFR, renal blood flow	↓Glomerulosclerosis, fibrosis	[50]
Coronary artery stenosis in pig	Anti-inflammatory antifibrotic	↓TNF-α, P67, GP91, TGF-β	↓Scr	↓Renal fibrosis, glomerular score, tubular injury	[58]
UUO in rat	Antioxidative	↓Caspase 3, HO-1, p38 MAPK, NF-κB-p65	NA	↓Interstitial fibrosis, tubular apoptosis↑ tubular proliferation	[44]
UUO in rat	Mitochondrial protection, antioxidative, antiapoptotic	↓Collagen I, fibronectin, α-SMA, mtROS, caspase 3,7,9	NA	↓Renal fibrosis, tubular apoptosis	[59]
Uninephrectomy and STZ-induced CD1 mice	Antioxidative; Antiapoptotic	↓Nox4, TXNIP, TGF-β, fibronectin, collagen IV, Bax, p38 MAPK, CREB ↑Bcl-2	↓Proteinuria, urinary 8-OHdG	↓Glomerular hypertrophy, mesangial expansion	[15]
STZ-induced C57BL/6 mice	Mitochondrial protection	↓Drp1, Bax, caspase 1, IL-1β ↑Mfn1, MDA ↑SOD, GSH-PX, Bcl-2,	↓Proteinuria, Scr, BUN	↓Tubulointerstitial fibrosis, mesangial matrix proliferation	[60]
db/db mouse	Mitochondrial protection	↓Pla2; ↑LCLAT1, Mfn1	↓Albuminuria, urinaryH2O2, urinary ACR	↓Mesangial matrix accumulation	[52]
db/db mice	Antioxidative, antilipid deposition	↑ MnSOD, CAT; ↓NADPH oxidase, CD36, fibronectin, collagen IV, NF-κB	↓Proteinuria, Scr, urinary 8-OHdG, urinary MDA	↓Glomerular hypertrophy, tubular injury	[42]
BTBR^ob/ob and Abca1^fl/fl ob/ob mice	Mitochondrial protection	NA	↓ACR, BUN, Scr, albuminuria	↑Podocyte number ↓mesangial expansion	[51]
HFD-induced C57BL/6	Mitochondrial protection, antiapoptotic, anti-inflammatory	↓TNF-α, MCP-1, NF-κB, VEGF, TGF-β↑p-AMPK	NA	↓Glomerulosclerosis, mesangial expansion; ↑podocytes, endothelial cells	[23]
Diet-induced MetS in pig	Mitochondrial protection	↑PPAR-α, P62, Bcl-xl ↓caspase 3	Scr, GFR (no effect)	↓Medullary volume, medullary hypoxia	[61]

IR: ischemia-reperfusion; AKI: acute kidney injury; STZ: streptozocin; Scr: serum creatinine; Ccr: creatinine clearance; BUN: blood urea nitrogen; GFR: glomerular filtration rate; GSH: glutathione; MDA: malondialdehyde; HO-1: heme oxygenase-1; iNOS: nitric oxide synthase; MPO: myeloperoxidase; TNF-α: tumor necrosis factor-alpha; NF-κB: nuclear factor kappa B; TGF-β: transforming growth factor-β; SOD: superoxide dismutase; ROS: reactive oxygen species; FeNa%: fractional excretion of sodium; FeK%: fractional excretion of potassium; MCP-1: monocyte chemoattractant protein; PGCα: peroxisome. Proliferator–activated receptor-γ-coactivator; PPAR-α: peroxisome proliferator–activated receptor; VEGF: vascular endothelial growth factor; UUO: unilateral ureteral obstruction; mtROS: mitochondrial ROS; TXNIP: thioredoxin-interacting protein; 8-OHdG: 8-hydroxy-2-deoxyguanosine; ACR: albumin to creatinine ratio; Pla2: phospholipase A2; LCLAT1: lysocardiolipin acyltransferase 1; MnSOD: Mn superoxide dismutase; CAT: catalase; HFD: high-fat diet; MetS: metabolic syndrome; NA: not described.