Effects and mechanisms of UCG ameliorating renal interstitial fibrosis by regulating TGF-β1/SnoN/Smads signaling pathway in renal failure rats

Abstract

This study was aimed to demonstrate preliminarily the effects and mechanisms of uremic clearance granule (UCG) ameliorating renal interstitial fibrosis (RIF) by regulating transforming growth factor (TGF)-β1/SnoN/Smads signaling pathway in vivo. Fifteen rats were randomly divided into 3 groups：the normal group,the model group and the UCG group. The rats with renal failure were induced by intragastric administration of adenine and unilateral ureteral obstruction (UUO). After modeling,the rats in the UCG group and in the other groups were intervened by intragastric administration of UCG and distilled water respectively during 3 weeks. The body weight and 24 h urinary protein excretion (Upro) in all rats were tested after drug administration. All rats were killed after drug administration for 3 weeks,blood and kidneys were collected and weighted,kidney appearance and renal morphological characteristics were observed. In addition,serum biochemical indices and the protein expressions of TGF-β1,SnoN,phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in the kidney were evaluated respectively. The results indicated that,after the intervention of UCG,the general state of health,kidney appearance,serum creatinine (Scr),blood urea nitrogen (BUN),uric acid (UA),albumin (Alb),Upro and renal morphological change in model rats were improved in different degrees,respectively. Moreover,UCG down-regulated the protein expressions of TGF-β1 and p-Smad2/3,and up-regulated the protein expressions of SnoN and Smad7 in the kidney. In conclusion,UCG reduces extracellular matrix (ECM) synthesis and delays the progression of renal failure via possibly multi-targeting at regulating TGF-β1/SnoN/Smads signaling pathway in vivo.