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Horm Metab Res 2009; 41(8): 605-611
DOI: 10.1055/s-0029-1220736
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

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

C. H. Yeh 1 , 5 , C. K. Chang 2 , M. F. Cheng 3 , H. J. Lin 4 , J. T. Cheng 1 , 4 , 5
  • 1Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
  • 2Department of Surgery, Mackay Memorial Hospital, and Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei City, Taiwan
  • 3Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan City, Taiwan
  • 4Department of Emergency Medicine and Department of Medical Research, Chi-Mei Medical Center, Yung Kang City, Tainan Shen, Taiwan
  • 5Institute of Medical Science, College of Health Science, Chang Jung Christian University, Kway Jean, Tainan, Taiwan, R.O.C.
Further Information

Publication History

received 06.02.2009

accepted 31.03.2009

Publication Date:
13 May 2009 (online)

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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
    Search in Google Scholar
  • 2 Simic P, Vukicevic S. Bone morphogenetic proteins in development and homeostasis of kidney.  Cytokine Growth Factor Rev. 2005;  16 299-308
    Search in Google Scholar
  • 3 Mitu G, Hirschberg R. Bone morphogenetic protein-7 (BMP7) in chronic kidney disease.  Front Biosci. 2008;  13 4726-4739
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 11 Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy.  J Am Soc Nephrol. 2005;  16 ((Suppl 1)) S30-S33
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 13 Shah SV, Baliga R, Rajapurkar M, Fonseca VA. Oxidants in chronic kidney disease.  J Am Soc Nephrol. 2007;  18 16-28
    Search in Google Scholar
  • 14 Lehmann R, Schleicher ED. Molecular mechanism of diabetic nephropathy.  Clin Chim Acta. 2000;  297 135-144
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 21 Mauer SM, Steffes MW, Brown DM. The kidney in diabetes.  Am J Med. 1981;  70 603-612
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 28 Sharma S, Anjaneyulu M, Kulkarni SK, Chopra K. Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats.  Pharmacology. 2006;  76 69-75
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 30 Tsilibary EC. Microvascular basement membranes in diabetes mellitus.  J Pathol. 2003;  200 537-546
    Search in Google Scholar

Correspondence

Prof. J-T. ChengPhD, FCP 

Department of Pharmacology

College of Medicine

National Cheng Kung University

Tainan City

70101 Taiwan

Phone: +886/6/237 27 06

Fax: +886/6/238 65 48

Email: jtcheng@mail.ncku.edu.tw