intervention effect of ursolic acid on renal fibrosis by regulating TGF-β1/Smads signaling pathway

OBJECTIVE To observe the effect of ursolic acid on renal fibrosis and renal tubular epithelial-mesenchymal transdifferentiation(EMT) in mice induced by unilateral ureteral obstruction(UUO), and to explore the role of TGF-β1/Smads signaling pathway. METHODS Fifty ICR male mice were randomly divided into 5 groups:sham operation group, model group, low-dose, medium-dose and high-dose ursolic acid groups, 10 in each group. The mouse kidney fibrosis model was created by unilateral ureteral ligation, and continuous intragastric administrated with different doses of ursolic acid for 7 d after operation. After the administration, the mouse serums were collected to determine the biochemical indicators(creatinine and urea nitrogen). The mice were sacrificed and left obstructed kidney tissue specimens were collected. Pathological staining (HE and Masson staining) was performed to observe the degree of renal tissue fibrosis. Immunohistochemical staining and Western blotting were used to determine expression of the EMT marker protein(E-cadherin and α-SMA), TGF-β1 and p-Smad2/3. RESULTS Compared with model group, in different dose of ursolic acid groups, the creatinine and urea nitrogen levels significantly decreased, the collagen deposition was significantly reduced, the degree of inflammatory cell infiltration was significantly improved, the expression level of E-cadherin increased significantly, α-SMA decreased significantly, TGF-β1 and p-Smad2/3 expression levels were significantly reduced. CONCLUSION Ursolic acid can reduce renal fibrosis and renal tubular EMT. Its protective effect mechanism may be related to the inhibition of TGF-β1/Smads signaling pathway.