Effect of valsartan on expression of osteopontin and bone morphogenetic protein-7 in kidneys of type 2 diabetic rats
Ruixia Ma
Abstract
Ruixia Ma
Abstract
Objective To investigate the effect of valsartan on ostcopontin(OPN) and bone morphogenetic protein-7(BMP-7) in the kidneys of type 2 diabetic mellitus(T2DM) rats.Methods Wistar rats were divided into control.T2DM.and valsartan treatment [25 mg/(kg·d)]groups.Rats were fed high sucrose high fat diet combined with a low dose of streplozotocin(STZ) to induce T2DM models.After administration of valsartan for 12 weeks,blood pressure,blood glucose,urinary albumin(UAL) and creatinine clearance(CCr) were determined.Renal morphology was observed under light microscope.The protein and mRNA expressions of BMP-7,OPN,transforming growth factor-β_1(TGF-β_1),fibronectin and ED-1 in renal tissue were determined by immunohistochemistry and quantitative real time PCR respectively.Results Compared with control group,in T2DM rats,UAL was significantly increased(P0.01);the expressions of BMP-7 protein and mRNA were significantly decreased(P0.01);the expressions of OPN,fibronectin and TGF-β_1 were elevated(P0.01).UAL was markedly attenuated by valsartan(P0.01).Valsartan effectively suppressed the expressions of fibronectin.OPN and TGF-β_1 and decreased ED-1 positive cells(P0.05),while significantly upregulated the expressions of BMP-7(P0.01).Conclusion Valsartan has protective effects on diabetic nephropathy by decreasing macrophage infiltration and reducing extracellular matrix accumulation,which may involve the down regulation of TGF-β_1 and OPN, as well as recovery of BMP-7.
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Objective To investigate the effect of valsartan on ostcopontin(OPN) and bone morphogenetic protein-7(BMP-7) in the kidneys of type 2 diabetic mellitus(T2DM) rats.Methods Wistar rats were divided into control.T2DM.and valsartan treatment [25 mg/(kg·d)]groups.Rats were fed high sucrose high fat diet combined with a low dose of streplozotocin(STZ) to induce T2DM models.After administration of valsartan for 12 weeks,blood pressure,blood glucose,urinary albumin(UAL) and creatinine clearance(CCr) were determined.Renal morphology was observed under light microscope.The protein and mRNA expressions of BMP-7,OPN,transforming growth factor-β_1(TGF-β_1),fibronectin and ED-1 in renal tissue were determined by immunohistochemistry and quantitative real time PCR respectively.Results Compared with control group,in T2DM rats,UAL was significantly increased(P0.01);the expressions of BMP-7 protein and mRNA were significantly decreased(P0.01);the expressions of OPN,fibronectin and TGF-β_1 were elevated(P0.01).UAL was markedly attenuated by valsartan(P0.01).Valsartan effectively suppressed the expressions of fibronectin.OPN and TGF-β_1 and decreased ED-1 positive cells(P0.05),while significantly upregulated the expressions of BMP-7(P0.01).Conclusion Valsartan has protective effects on diabetic nephropathy by decreasing macrophage infiltration and reducing extracellular matrix accumulation,which may involve the down regulation of TGF-β_1 and OPN, as well as recovery of BMP-7.
Key concepts: Valsartan, Osteopontin, Medicine, Endocrinology, Internal medicine, Diabetic nephropathy, Fibronectin, Osteoprotegerin