Decrease of Bone Morphogenetic Protein-7 (BMP-7) and its Type II Receptor (BMP-RII) in Kidney of Type 1-Like Diabetic Rats

Abstract

Bone morphogenetic protein-7 (BMP-7) expression is known to be protective for renal damage during diabetic nephropathy and disappears early during the progression of diabetic nephropathy. However, changes in expression of BMP-7 and BMP-7 type II receptor (BMP-RII) during kidney nephropathy response to high glucose-induced oxidative stress remain unclear. In this study, we used streptozotocin-induced diabetic rats with diabetic nephropathy and treated them with insulin, phloridzin, or antioxidant tiron. The insulin, phloridzin, or tiron treatment improved the renal function and decreased fibronectin expression in the streptozotocin-induced diabetic rats. Both insulin and phloridzin could reverse the attenuation effects of hyperglycemia on BMP-7 and BMP-RII expressions in the kidneys of streptozotocin-induced diabetic rats through the correction of hyperglycemia. However, the decrease of BMP-7 and BMP-RII expressions in kidney of streptozotocin-induced diabetic rats could be reversed by tiron through decreasing the high glucose-induced oxidative stress but not through changing the levels of glucose. We further confirmed the effect on reversing the BMP-7 and BMP-RII expressions through decreasing oxidative stress by tiron treatment in high glucose exposed mesangial cells. Thus, we suggest that a decrease in oxidative stress is responsible for the improvement of renal function and recovery of renal BMP-7 and BMP-RII expression in streptozotocin-induced diabetic rats.

Key words

BMP-7 - BMP-RII - diabetic nephropathy - oxidative stress

References

• 1 Kitten AM, Kreisberg JI, Olson MS. Expression of osteogenic protein-1 mRNA in cultured kidney cells.  J Cell Physiol. 1999;  181 410-415
• 2 Simic P, Vukicevic S. Bone morphogenetic proteins in development and homeostasis of kidney.  Cytokine Growth Factor Rev. 2005;  16 299-308
• 3 Mitu G, Hirschberg R. Bone morphogenetic protein-7 (BMP7) in chronic kidney disease.  Front Biosci. 2008;  13 4726-4739
• 4 Hruska KA, Guo G, Wozniak M, Martin D, Miller D, Liapis, Loveday K, Klahr S, Sampath TK, Morrissey J. Osteogenic protein-1 prevents renal fibrogenesis associated with ureteral obstruction.  Am J Physiol Renal Physiol. 2000;  279 F130-F143
• 5 Wang S, Chen Q, Simon TC, Strebeck F, Chaudhary L, Morrissey J, Liapis H, Klahr S, Hruska KA. Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy.  Kidney Int. 2003;  63 2037-2049
• 6 Wang SN, Lapage J, Hirschberg R. Loss of tubular bone morphogenetic protein-7 in diabetic nephropathy.  J Am Soc Nephrol. 2001;  12 2392-2399
• 7 Bosukonda D, Shih MS, Sampath KT, Vukicevic S. Characterization of receptors for osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7) in rat kidneys.  Kidney Int. 2000;  58 1902-1911
• 8 Qian Y, Feldman Y, Pennathur S, Kretzler M, Brosius 3rd FC. From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy.  Diabetes. 2008;  57 1439-1445
• 9 Lund RJ, Davies MR, Hruska KA. Bone morphogenetic protein-7: an anti-fibrotic morphogenetic protein with therapeutic importance in renal disease.  Curr Opin Nephrol Hypertens. 2002;  11 31-36
• 10 Vukicevic S, Basic V, Rogic D, Casic N, Shih MS, Shepard A, Jin D, Dattatreyamury B, Jones W, Dorai H, Rayn S, Griffiths D, Maliakal J, Jelic M, Pastorcic M, Stavljenic A, Sampath KT. Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.  J Clin Invest. 1998;  102 202-214
• 11 Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy.  J Am Soc Nephrol. 2005;  16 ((Suppl 1)) S30-S33
• 12 Ohkubo YK, Araki H, Miyata E, Isami T, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.  Diabetes Res Clin Pract. 1995;  28 103-117
• 13 Shah SV, Baliga R, Rajapurkar M, Fonseca VA. Oxidants in chronic kidney disease.  J Am Soc Nephrol. 2007;  18 16-28
• 14 Lehmann R, Schleicher ED. Molecular mechanism of diabetic nephropathy.  Clin Chim Acta. 2000;  297 135-144
• 15 Ha H, Lee HB. Reactive oxygen species amplify glucose signalling in renal cells cultured under high glucose and in diabetic kidney.  Nephrology (Carlton). 2005;  10 ((Suppl)) S7-S10
• 16 Cheng JT, Huang CC, Liu IM, Tzeng TF, Chang CJ. Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats.  Diabetes. 2006;  55 819-825
• 17 Huang CJ, Liu IM, Cheng JT. Increase of peroxisome proliferator-activated receptor delta gene expression in the lungs of streptozotocin-induced diabetic rats.  Pulm Pharmacol Ther. 2007;  20 69-74
• 18 Hsieh TJ, Zhang SL, Filep JG, Tang SS, Ingelfinger JR, Chan JS. High glucose stimulates angiotensinogen gene expression via reactive oxygen species generation in rat kidney proximal tubular cells.  Endocrinology. 2002;  143 2975-2985
• 19 Iglesias-De La Cruz MC, Ruiz-Torres P, Lcami J, Diez-Marques L, Ortega-Velazquez R, Chen S, Rodriguez-Puyol M, Ziyadeh FN, Rodriguez-Puyol D. Hydrogen peroxide increases extracellular matrix mRNA through TGF-beta in human mesangial cells.  Kidney Int. 2001;  59 87-95
• 20 Xia L, Wang H, Goldberg HJ, Munk S, Fantus IG, Whiteside CI. Mesangial cell NADPH oxidase upregulation in high glucose is protein kinase C dependent and required for collagen IV expression.  Am J Physiol Renal Physiol. 2006;  290 F345-F356
• 21 Mauer SM, Steffes MW, Brown DM. The kidney in diabetes.  Am J Med. 1981;  70 603-612
• 22 Hawkins M, Hu M, Yu J, Eder H, Vuguin P, She L, Barzilai N, Leiser M, Backer JM, Rossetti L. Discordant effects of glucosamine on insulin-stimulated glucose metabolism and phosphatidylinositol 3-kinase activity.  J Biol Chem. 1999;  274 31312-31319
• 23 Mitu GM, Wang S, Hirschberg R. BMP7 is a podocyte survival factor and rescues podocytes from diabetic injury.  Am J Physiol Renal Physiol. 2007;  293 F1641-F1648
• 24 Matsumoto K, Puia G, Dong E, Pinna G. GABA(A) receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders.  Stress. 2007;  10 3-12
• 25 Lee HB, Yu MR, Yang Y, Jiang Z, Ha H. Reactive oxygen species-regulated signaling pathways in diabetic nephropathy.  J Am Soc Nephrol. 2003;  14 S241-S245
• 26 Heyman SN, Khamaisi M, Rosen S, Rosenberger C. Renal parenchymal hypoxia, hypoxia response and the progression of chronic kidney disease.  Am J Nephrol. 2008;  28 998-1006
• 27 Koya D, Hayashi K, Kitada M, Kashiwagi A, Kikkawa R, Haneda M. Effects of antioxidants in diabetes-induced oxidative stress in the glomeruli of diabetic rats.  J Am Soc Nephrol. 2003;  14 S250-S253
• 28 Sharma S, Anjaneyulu M, Kulkarni SK, Chopra K. Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats.  Pharmacology. 2006;  76 69-75
• 29 Manabe E, Handa O, Naito Y, Mizushima K, Akagiri S, Adachi S, Takagi T, Kokura S, Maoka T, Yoshikawa T. Astaxanthin protects mesangial cells from hyperglycemia-induced oxidative signaling.  J Cell Biochem. 2008;  103 1925-1937
• 30 Tsilibary EC. Microvascular basement membranes in diabetes mellitus.  J Pathol. 2003;  200 537-546

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