N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal inflammation and tubulointerstitial fibrosis in rats.
It has been reported that N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) attenuates renal and cardiac inflammation as well as fibrosis in hypertensive rats. In this study, we investigated these effects using a unilateral ureteral obstruction (UUO) model. Eighteen male Wistar rats were randomly divided into three groups: control, UUO/vehicle and UUO/Ac-SDKP groups. Animal models of renal inflammation and tubulointerstitial fibrosis were established with unilateral ureteral ligation in rats. Ac-SDKP and vehicle were infused subcutaneously by using osmotic mini pumps for two weeks. On the 14th day post-injection, kidney histological changes of each group were observed by hematoxylin-eosin and Masson's stain. Renal macrophage infiltration, together with protein expression and localization of monocyte chemoattractant protein-1 (MCP-1), nuclear factor-kappa B (NF-κB), α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in renal tissue was assessed by immunohistochemical staining. Gene expression of MCP-1 and TGF-β1 was analyzed with reverse transcription-polymerase chain reaction. Ac-SDKP-treated animals demonstrated less severe renal inflammation and tubulointerstitial fibrosis. Interstitial fibrosis was significantly attenuated with Ac-SDKP. ED-1 was expressed in the interstitium of the UUO/vehicle group kidneys and decreased with Ac-SDKP treatment. MCP-1, NF-κB, α-SMA and TGF-β1 were increased in the renal interstitium and tubular epithelial cells of the UUO/vehicle group. Ac-SDKP significantly reduced their expressions. Gene expressions of MCP-1 and TGF-β1 were upregulated in the UUO/vehicle group kidneys and were significantly inhibited by Ac-SDKP. In conclusion, in the rat UUO model Ac-SDKP administration protected against renal inflammation and tubulointerstitial fibrosis. The inhibitory effect of Ac-SDKP was mediated by the reduction in the expression of MCP-1, NF-κB, α-SMA and TGF-β1.
Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.
Mingao
M
Wang
Ruichan
R
Liu
Xibei
X
Jia
Suhong
S
Mu
Rujuan
R
Xie
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009393:Nephritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; C058504:goralatide