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Liu, B.C. et al.

Bi-cheng Liu, Hui-ling Xia, Ji-ning Wu, Xiao-liang Zhang, Dian-ge Liu, Yu-xiang Gong,

Influence of irbesartan on expression of ILK and its relationship with epithelial-mesenchymal transition in mice with unilateral ureteral obstruction.

AIM: Irbesartan, a new antagonist of the type 1 angiotensin II receptor, has been proven to be renal protective in both diabetic and non-diabetic nephropathy, but its exact mechanism is still uncertain. Here we investigated the influence of irbesartan on the expression of the integrin-linked kinase (ILK) and its relationship with epithelial-mesenchymal transition (EMT) in mice with unilateral ureteral obstruction (UUO). METHODS: The mice were randomly divided into 3 groups: sham operation (C, n=20), UUO (n=40), and UUO with irbesartan treatment (UUO+irbesartan, n=40). Irbesartan was given at a dose of 50 mg/kg body weight per day by gavage. The experimental animals in the control group received the same volume of vehicle (0.9% saline solution). The animals were sacrificed at d 1, 3, 7, and 14, respectively, after the surgery. RESULTS: The expression of the ILK at mRNA and protein levels were significantly increased in the UUO group 1 d after the surgery, which was significantly decreased by treatment with irbesartan (P<0.01, respectively). The expression of alpha-smooth muscle actin (alpha-SMA) was significantly increased, while E-cadherin was decreased in mice with UUO at d 3 after the surgery. Treatment with irbesartan significantly abrogated such effects (P<0.01). The immunohistochemistry analysis indicated that the protein expression of the ILK was positively correlated with alpha-SMA, but negatively with E-cadherin. CONCLUSION: These results suggested that irbesartan attenuated renal tubulointerstitial fibrosis in UUO mice, which may be related to the inhibition of ILK expression, subsequently preventing the tubular EMT.[1]

References

Influence of irbesartan on expression of ILK and its relationship with epithelial-mesenchymal transition in mice with unilateral ureteral obstruction. Liu, B.C., Xia, H.L., Wu, J.N., Zhang, X.L., Liu, D.G., Gong, Y.X. Acta Pharmacol. Sin. (2007) [Pubmed]

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