Effects and mechanism of irbesartan on tubulointerstitial fibrosis in 5/6 nephrectomized rats.
Tubulointerstitial fibrosis (TIF) is a common pathological feature of end-stage kidney disease. Previous studies showed that upregulation of TGFbeta1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction. This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFbeta1 in the rodent model of chronic renal failure involving 5/6 nephrectomy. The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model. Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group, but the lesion was attenuated mostly in irbesartan-treated group. Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFbeta1 which was up-regulated in operation groups. Western blot showed that irbesartan treatment down-regulated the expression of TGFbeta1, phosphorylated smad2 (p-smad2), AT1R and phosphorylated p38 (p-p38) MAPK, but significantly up-regulated the protein expression of smad6 as compared with operation group. These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6, TGF-beta1, p-smad2, AT1 and p-p38 MAPK.
The Institute of Hypertension and Cardiovascular Division, Department of Internal Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China. zg000507@163.com
Gang
G
Zhao
Hong
H
Zhao
Ling
L
Tu
Xizhen
X
Xu
Changlong
C
Zheng
Meihua
M
Jiang
Peihua
P
Wang
Daowen
D
Wang
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis / Q000517:prevention & control; D000077405:Irbesartan; D007674:Kidney Diseases / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D009392:Nephrectomy; D009400:Nephrosclerosis / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D051905:Smad6 Protein / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D051905:Smad6 Protein; C497804:Smad6 protein, rat; D013777:Tetrazoles; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; D000077405:Irbesartan