Open AccessInfluence of irbesartan on expression of ILK and its relationship with epithelial‐mesenchymal transition in mice with unilateral ureteral obstruction
Author(s) -
LIU Bicheng,
XIA Huiling,
WU Jining,
ZHANG Xiaoliang,
LIU Diange,
GONG Yuxiang
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00649.x
Subject(s) - irbesartan , epithelial–mesenchymal transition , medicine , endocrinology , diabetic nephropathy , fibrosis , urology , kidney , cancer , blood pressure , metastasis
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 α‐smooth muscle actin (α‐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 α‐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.