Proteklnuria reduction via regulation of oxidative stress produced by podocytes in diabetic nephropathy

• Project/Area Number: 14571014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: TOJO Akihiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (50292917)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
• Keywords: diabletic nephropathy / HADP-H oxidase / nitric oxide / superoxide / angiotensin II / podocyte / proteinuria / Oxidative stress / oxidative stress / NOS / microalbuminuria / angiotensin

Research Abstract

In this study, we investigated the effect of inhibition of oxidative stress produced by podocytes in diabetic nephropathy. Podocytes express classic phagocytic NADPH oxidase and NADPH oxidase expression and superoxide production were increased in the streptozotocin-induced diabetic rats as well as in hypertensive rats.
NADPH oxidase is regulated by angiotensin II, TNF-a and IL-1f3, and ACE inhibitor, ATI receptor blocker (ARB) as well as p38 MAPI( inhibitor suppressed the expression of NADPH oxidase, decreased renal radical production and ameliorated microalbuminuria. The suppression of platelet-derived cytokines by dipyridamole contributed to the suppression of NADPH oxidase and enhanced NOS expression to maintain microcirculation. The NADPH oxidase inhibitor, apocynin showed a stronger inhibition of radical production in the kidney than SOD and decreased proteinuria.
As nephrin is located in the lipid raft of podocyte's membrane, a high cholesterol condition may have some influence in nephrin expression in the podocyte and its barrier function in proteinuria. Diabetic rat fed with a high cholesterol diet showed enhanced expression of NNDPH oxidase in podocytes as well as enhanced ICAM-1 expression in the glomerular endothelial cells with enhanced microphage migration. Gliclazide has been attributed an anti-oxidant effect due to its azabicyclo-octyl ring, this drug showed significant reduction of oxidative stress by suppression of renal NADPH oxidase and macrophage migration and consequently reduced proteinuria compared to glibenclamide that has no effect on radical reduction.
Incubation of podocytes from isolated glomeruli with angiotensin II showed changes in NADPH oxidase expression and actin distribution, and these changes may regulate nephrin expression in podocytes, but we have not reached a conclusion yet.
Microalbuininuria is not only regulated by poclocyte function but also by endocytosis of albumin in the proximal convoluted tubules via megalin. ACE inhibitor and ARB up-regulated megalin expression in proximal tubule and ameliorated endocytosis of albumin and reduced microalbuminuria in diabetic rat.
In conclusion, reduction of NADPH oxidase expression in podocytes and its products using various interventions have an important role to reduce proteinuria in diabetic nephropathy.

Research Products

• [Publications] Maristela Lika Onozato, Akihiro Tojo, Atsuo Goto, Toshiro Fujita: "Radical scavenging effect of gliclazide in diabetic rats fed with a high cholesterol diet"Lidney Int. 65(3). 951-960 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tojo Atsuo, Onozato ML, Kobayashi N, Goto A, Matsuoka H, Fujita T: "Angiotensin II and Oxidative Stress in Dahl Salt-Sensitive Rat With Heart Failure."Hypertension. 40. 834-839 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tojo A, Onozato ML, Kurihara H, Sakai T, Goto A, Matsuoka H, Fujita T: "Angiotensin II Blockade Restores Albumin Readsorption in Proximal Tubule of Diabetic Rat."Hypertens Res. 26. 413-419 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Onozato ML, Tojo A, Goto A, Fujita T: "Effect of combination therapy with dipyridamole and quinapril in diabetic nephropathy."Diabetes Res Clin Pract. 59. 83-92 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tojo A, Fujita T, Wilcox CS: "Omapatrilat : still a promise in salt-sensitive hypertension?"J Hypertens. 21(1). 31-32 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Onozato ML, Tojo A, Goto A, Fujita T, Wilcox CS: "Oxidative stress and NOS in rat diabetic nephropathy : Effects of ACEI orARB"Kidney Int. 61. 186-194 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Chabrashivili T, Tojo A, Onozato ML, Kitiyakara C, Quinn MT, Fujita T, Welch WJ, Wilcox CS: "Expresson and Cellular Locailzation of Classic NADPH Oxidase Subunits in the Spontaneously Hypertensive Rat Kidney."Hypertension. 39. 269-274 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawai J, Ando K, Tojo A, Shimosawa T, Takahashi K, Onozato ML, Yamasaki M, Ogita T, Nakaoka T, Fujita T: "Endogenous Adrenomedullin Protects Against Vascular Response to Injury in Mice"Circulation. Feb 9. (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamasaki M, Kawai J, Nakaoka T, Ogita T, Tojo A, Fujita T: "Adrenomedullin overexpression to inhibit cuff-induced arterial intimal formation"Hypertension. 41(2). 302-307 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ueno T, Kaname S, Takaichi K, Nagase M, Tojo A, Onozato ML, Fujita T: "Lox-1, an oxidized low-density lipoprotein receptor, was upregulated in the kidneys of chronic renal failure rats."Hypertens Res. 26. 117-122 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Kakori M, Nagata D, Hayakawa H, Satonaka H, Sata M, Tojo A, Suzuki E, Kangawa K, Matsuo H, Kitamura T, Nagai R: "Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury : studies on transgenic/knockout mice of adrenomedullin gene."Circ Res. 90(5). 657-663 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Nagai R: "Hematopoietic stem cells that participate in the patho-genesis of atherosclerosis."Nat Med. 8(4). 403-409 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Enomoto A, Takeda M, Tojo A, Sekine T, Cha SH, Takayama F, Niwa T, Endou H: "Role of organic anion transporters in the uptake and toxicity of indoxyl sulfate"J.Am.Soc.Nephrol. 13. 1711-1720 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takeda M, Noshiro R, Onozato ML, Tojo A, Huang XL, Narikawa S, Endou H: "Evidence for a role of human organic anion transporters in the muscular side effect of HMG-G-CoA reductase inhibitors."Eur J Pharmacol. 483(2-3). 133-138 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kazuhisa MIYASHITA, Akihiro TOJO, Kenjiro KIMURA, Atsuo Goto, Masao OMATA, Keisuke NISHIYAMA, Toshiro FUJITA: "Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients."Hypertens Res. 27. 79-84 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Onozato ML, Tojo A, Ogura S, Asaba K, Goto A, Fujita T: "Primary amyloidosis with multiple pulmonary nodular lesions and IgAnephropathy-like renal involvement."Clin Nephrol. 60. 134-138 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H: "Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics."Eur J Pharmacol. 465(1-2). 1-7 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hasannejad H, Takeda M, Taki K, Jung SH, Babu E, Jutabha P, Khamdang S, Alegoyeh M, Onozato ML, Tojo A, Enomoto A, Anzai N, Narikawa S, Huang XL, Niwa T, Endou H: "Interactions of human organic anion transporters with diuretics"J Pharmacol Exp Ther. Nov.10. (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Asaba K, Tojo A, Onozato ML, Mimura N, Kido M, Goto A, Endo H, Fujita T: "Fibrillary glomerulonephritis associated With essential thrombocytosis"Clin Exp Nephrol. 7. 296-300 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Alebouyeh M, Takeda M, Onozato ML, Tojo A, Noshiro R, Hasannejad H, Inatomi J, Narikawa S, Huang XL, Khamdang S, Anzai N, Endou H: "Expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites."J Pharmacol Sci.. 93(4). 430-436 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Mise N, Kimura K, Kurabayashi M, Nagai R, Okuda T, Ohba S, Suzuki N, Miyashita K, Kamijo A, Tojo A, Omata M: "Angiotensin II Enhances Glomerular Expression of a Nonmuscle Myosin Heavy Chain, SMemb, with Extracellular Matrix Accumulation"Nephron. 90(4). 477-483 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Jung KY, Takeda M, Shimoda M, Narikawa S, Kim DK, Tojo A, Sekine T, Endou H: "Role of organic anion transporter 3 (OAT3) in cephaloridine-induced nephrotoxicity."Life Sci. 70. 1861-1874 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Hitoshi Endou H: "Characterization of ochratoxin A transport by human organic anion transporter 4.Biochim."Biophys Acta. 1590. 64-75 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 藤乗嗣泰, 小野里マリステラリカ, 浅羽研介: "NO : nitric oxide. Annual Review腎臓2004(伊藤克己, 遠藤仁, 御手洗哲也, 東原英二, 秋澤忠男 編)"中外医学社. 251(1-8) (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Maristela Lika Onozato, Akihiro Tojo, Atsuo Goto, Toshiro Fujita.: "Radical scavenging effect of gliclazide in diabetic rats fed with a high cholesterol diet."Kidney Int. 65(3). 951-960 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tojo A, Onozato ML, Kobayashi N, Goto A, Matsuoka H, Fujita T.: "Angiotensin II and Oxidative Stress in Dah1 Salt-Sensitive Rat With Heart Failure"Hypertension. 40. 834-839 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tojo A, Onozato ML, Kurihara H, Sakai T, Goto A, Fujita T.: "Angiotensin II Blockade Restores Albumin Reabsorption in Proximal Tubule of Diavetic Rat."Hypertens Res. 26. 413-419 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Onozato ML, Tojo A, Goto A, Fujita T.: "Effect of combination therapy with dipyridamole and quinapril in diabetic nephropathy."Diavetes Res Clin Pract. 59. 83-92 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tojo A, Fujita T, Wilcox CS.: "Omapatrilat: stil a promise in salt-sensitive hypertension?"J Hypertens. 21(1). 31-32 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Onozato ML, Tojo A Goto A, Fujita T, Wilcox CS.: "Oxidative stress and NOS in rat diavetic nephropathy Effects of ACEI or ARB."Kidney Int. 61. 185-194 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Chabrashyili T, Tojo A, Onozato ML, Kitiyakaara C, Quinn MT, Fujita T, Welch WJ, Wilcox CS.: "Expression and Cellular Localization of Classic NADPH Oxidase Subunits in the Spontneously Hypertensive Rat Kidney."Hypertension. 39. 259-274 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kawai J, Ando K, Tojo A.Shimosawa T, Takahashi K, Onozato ML, Yamasaki M, Ogita T, Nakaoka T, Fujita T.: "Endogenous Adrenomedullin Protects Against Vascular Response to Injury in Mice."Circulation. (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamasaki M, Kawai J, Nakaoka T, Ogita T, TOjo A, Fujita T.: "Adrenomedullin overexpression to inhibit cuff-induced arterial intimal formation."Hypertension. 42(2). 302-307 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ueno T, Kaname S, Takaichi K, Nagase M, Tojo A, Onozato ML, Fujita T.: "Lox-1, an oxidized low-density lipoprotein receptor, was upregulated in the kidneys of chronic renal failure rats."Hypertension. 26. 117-122 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Kakoki M, Nagata D, Hayakawa H, Satonaka H, Sata M, Tojo A, Suzuki E, Kangawa K, Matsuo H, Kitamura T, Nagai R.: "Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury: studies on transgenic/knockout mice of adrenomedullin gene."Circ Res.. 90(6). 657-663 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sata M, Saiura A, Knisato A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Nagai R.: "Hematopoietic stem cells differentiate into vascular cells that participate in the patlio-genesis of atherosclerosis."Nat Med. 8(4). 403-409 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Enomoto A, Takeda M, Tojo A, Sekine T, Cha SH, Takayarna F, Niwa T, Endou H.: "Role of organic anion transporters in the uptake and toxicity of indoxyl sulfate."J.Am. Soc. Nephrol. 13. 1711-1720 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takeda M, Noshiro R, Onozato ML, Tojo A, Hasannejad H, Huang XL, Narikawa S, Endou H.: "Evidence for a role of human organic anion transporters in the muscular side effects of HMG-CoA reductase inhibitors."Eur J Pharmacol.. 483(2-3). 133-138 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kazuhisa MIYASHITA, Akihiro TOJO, Kenjiro KIMURA, Atsuo GOTO, Masao OMATA, Keisuke NISHIYAMA, Toshiro FUJITA: "Blood pressure response to erythropoietin injection hi hemodialysis and predialysis patients."Hypertens Res. 27. 79-84 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Onozato ML, Tojo A, Ogura S, Asaba K, Goto A, Fujita T: "Primary aniyloidosis with multiple pulmonary nodular lesions and IgAnephropathy-like renal involvement."Clin Nephrol. 60. 134-138 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H: "Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics"Eur J Pharmacol. 465(1-2). 1-7 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hasannejad H, Takeda M, Taki.K, Jung SH, Babu E, Jutabha P.Khamdang S, Aleboyeh M, Onozato ML, Tojo A, Enomoto A, Anzai N, Narikawa S, Huang XL, Niwa T, Endou H.: "Interactions of human organic anion transporters with diuretics."J Pharmacol Exp Ther.. (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Asaba K, Tojo A, Onozato ML, Mimura N, Kido M, Goto A, Endo H, Fujita T.: "Fibrillaiy glomerulonephritis associated with essential thrombocytosis."Clin Exp Nephrol. 7. 296-300 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Alebouyeh M, Takeda M, Onozato ML, Tojo A, Noshiro R, Hasannejad H, Inatomi J, Narikawa S, Huaijg XL, Khamdang S, Anzai N, Endou H.: "Expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites."J Pharmacol Sci. 93(4). 430-436 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Mise N, Kimura K, Kurabayashi M, Nagai R, Okuda T, Oliba S, Suzuki N, Miyasbita K, Kaniijo A, Tojo A, Goto A, Omata M.: "Angiotensin II Enhances Glomerular Expression of a Nonniuscle Myosin Heavy Chain, SMemb, with Extracellular Matrix Accumulation."Nephron. 90(4). 477-483 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Jung KY, Takeda M, Shimoda M, Narikawa S, Kim DK, Tojo A, Sekine T, Endou H.: "Role of organic anion transporter 3 (OAT3) in cephaloridine-induced neplirotoxicity."Life Sci.. 0. 1861-1874 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Babu E, Takeda M, Narikawa S, Kobayashi Y, Enoinoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Hitoshi Endon H.: "Characterization of ochratoxin A transport by human organic anion transporter 4. Biochim."Biophys. Acta. 1590. 64-75 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Maristela Lika Onozato, Akihiro Tojo, Atsuo Goto, Toshiro Fujita: "Radical scavenging effect of gliclazide in diabetic rats fed with a high cholesterol diet."Kidney Int. 65(3). 951-960 (2004)
• [Publications] Tojo A, Onozato ML, Kurihara H, Sakai T, Goto A, Fujita T: "Angiotensin II Blockade Restores Albumin Reabsorption in Proximal Tubule of Diabetic Rat."Hypertension Res. 26. 413-419 (2003)
• [Publications] Onozato ML, Tojo A, Goto A, Fujita T: "Effect of combination therapy with dipyridamole and quinapril in diabetic nephropathy."Diabetes Res Clin Pract. 59. 83-92 (2003)
• [Publications] Tojo A, Fujita T, Wilcox CS: "Omapatrilat : still a promise in salt-sensitive hypertension?"J Hypertens. 21(1). 31-32 (2003)
• [Publications] Yamasaki M, Kawai J, Nakaoka T, Ogita T, Tojo A, Fujita T: "Adrenomedullin overexpression to inhibit cuff-induced arterial intimal formation."Hypertension. 41(2). 302-307 (2003)
• [Publications] Ueno T, Kaname S, Takaichi K, Nagase M, Tojo A, Onozato ML, Fujita T: "Lox-1, an oxidized low-density lipoprotein receptor, was upregulated in the kidneys of chronic renal failure rats."Hypertens Res. 26. 117-122 (2003)
• [Publications] Takeda M, Noshiro R, Onozato ML, Tojo A, Hasannejad H, Huang XL, Narikawa S, Endou H: "Evidence for a role of human organic anion transporters in the muscular side effects of HMG-CoA reductase inhibitors."Eur J Pharmacol. 483(2-3). 133-138 (2004)
• [Publications] MIYASHITA K, TOJO A, KIMURA K, GOTO A, OMATA M, NISHIYAMA K, FUJITA T: "Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients."Hypertens Res. 27. 79-84 (2004)
• [Publications] Onozato ML, Tojo A, Ogura S, Asaba K, Goto A, Fujita T: "Primary amyloidosis with multiple pulmonary nodular lesions and IgA nephropathy-like renal involvement."Clin Nephrol. 60. 134-138 (2003)
• [Publications] Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H: "Interaction of human and at rat organic anion transporter 2 with various cephalosporin antibiotics."Eur J Pharmacol. 465(1-2). 1-7 (2003)
• [Publications] Asaba K, Tojo A, Onozato ML, Mimura N, Kido M, Goto A, Endo H, Fujita T: "Fibrillary glomerulonephritis associated with essential thrombocytosis."Clin Exp Nephrol. 7. 296-300 (2003)
• [Publications] Alebouyeh M, Takeda M, Onozato ML, Tojo A, Noshiro R, Hasannejad H, Inatomi J, Narikawa S, Huang XL, Khamdang S, Anzai N, Endou H: "Expression of human organic anion transporters in the choroid plexus and their interactions with neurotransmitter metabolites."J Pharmacol Sci.. 93(4). 430-436 (2003)
• [Publications] 藤乗嗣泰, 小野里マリステラリカ, 浅羽研介: "NO : nitric oxide. Annual Review腎臓2004"中外医学社(伊藤克己、遠藤仁、御手洗哲也、東原英二、秋澤忠男 編). 251(1-8) (2004)
• [Publications] TOJO A, ONOZATO ML.KURIHARA H, SAKAI T, GOTO A.FUJITA T: "Angiotensin II Blockade Restores Albumin Reabsorption in Proximal Tubule of Diabetic Rat"Hypertens Res.. 26(5)(in press). (2003)
• [Publications] Onozato ML, Tojo A, Goto A, Fujita T: "Effect of combination therapy with dipyridamole and quinapril in diabetic nephropathy"Diabetes Res. Clin. Pract.. 59(2). 83-92 (2003)
• [Publications] Ueno T, Kaname S, Takaichi K, Nagase M Tojo A, Onozato ML, Fujita T: "Lox-1, an oxidized low-density lipoprotein receptor, was upregulated in the kidneys of chronic renal failure rats"Hypertens Res.. 26(1). 117-122 (2003)
• [Publications] Akihiro Tojo, Toshiro Fujita, Christopher S: "Omapatrilat : still a promise in salt-sensitive hypertension?"J.Hypertens.. 21(1). 31-32 (2003)
• [Publications] Tojo A, Onozato ML., Kobayashi N, Goto A, Matsuoka H, Fujita T: "Angiotensin II and Oxidative Stress in Dahl Salt-Sensitive Rat With Heart Failure"Hypertension. 40(12). 834-839 (2002)
• [Publications] Onozato ML, Tojo A, Goto A, Fujita T, Wilcox CS: "Oxidative stress and NOS in rat diabetic nephropathy : Effects of ACEI or ARB"Kidney Int.. 61(1). 186-194 (2002)
• [Publications] Chabrasliviti T, Tojo A, Onozato ML, Kitiyyakara C, Qinn MT, Fujita T, Weleh WJ, Wilcox CS: "Expression and Cellular Localization of Classic NADPH Oxidase Subunits in the Spontaneously Hypertensive Rat Kidney"Hypertension. 39(2). 269-274 (2002)
• [Publications] Sata M, Saiura A Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Magai R: "Hematopoictic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis"Nature Medicine. 8(4). 403-409 (2002)
• [Publications] Jung KY, Takeda M, Shimoda M, Narikawa S, Kim DK, Tojo A, Sekine, TEndou H: "Role of organic anion transporter 3(OAT3) in cephaloridine-induced nephrotoxicity."Life Sci.. 70. 1861-1874 (2002)
• [Publications] Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: "Characterization of ochratoxin A transport by human organic anion transporter 4"Biochim. Biophys. Acta. 1590. 64-75 (2002)
• [Publications] Enomoto A, Takeda M, Tojo A, Sekine T, Cha SH, Takayama F, Niwa T, Endou H: "Role of organic anion transporters in the uptake and toxicity of indoxyl sulfate"J.Am, Soc. Nephrol.. 13. 1711-1720 (2002)
• [Publications] Mise N, Kimura k, Kurabayashi M, Nagai R, Okuda T, Ohba S, Suzuki N, Miyashita K, Kamijo A, Tojo A, Goto A, Omata M: "Angiotensin II Enhances Glomerular Expression of a Nonmuscle Myosin Heavy Chain, SMemb, with Extracellular Matrix Accumulation"Nephron. 90(4). 477-483 (2002)
• [Publications] Nishimatsu H, Hirata Y, Shindo T, Kurihara H, Kakoki M, Nagata D, Hayakawa H, Satonaka H, Sata M, Tojo A, Suzuki E, Kangawa K, Matsuo H, Kitamura T, Nagai R: "Role of endogenous adrenomedullin in the regulation of vascular tone and ischemic renal injury; studies on transgenic/knockout micc of adrenomedulin gene"Cire, Res.. 90(6). 657-663 (2002)
• [Publications] 藤乗嗣泰: "糖尿病による微小蛋白尿"腎と透析. 53. 587-592 (2002)
• [Publications] 藤乗嗣泰: "食塩と高血圧 -血圧調節機構の異常と食塩感受性高血圧:酸化ストレス-"日本医学出版、藤田敏郎 編集. 71-76 (2002)
• [Publications] 藤乗嗣泰: "腎臓病 専門医に聞く最新の臨床-腎疾患とエンドセリン、NOの関与-;-腎疾患とアポトーシス-"中外医学社(御手洗哲也、秋葉隆編集). 206-209 (2002)