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


CONCLUSIONS
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.
Liu
Bi-cheng
BC
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing 210009, China. liubc64@yahoo.com.cn
Xia
Hui-ling
HL
Wu
Ji-ning
JN
Zhang
Xiao-liang
XL
Liu
Dian-ge
DG
Gong
Yu-xiang
YX
D000199:Actins / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D054338:Cell Transdifferentiation / Q000187:drug effects*; D015536:Down-Regulation; D004847:Epithelial Cells; D005355:Fibrosis / Q000517:prevention & control*; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009395:Nephritis, Interstitial / Q000517:prevention & control; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013777:Tetrazoles / Q000494:pharmacology*; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology*; D000099200:Scaffold Protein ILK
D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D015820:Cadherins; D000077405:Irbesartan; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D013777:Tetrazoles; D000099200:Scaffold Protein ILK