Establishment of a novel therapy for proteinuria

• Project/Area Number: 20590950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: KAWACHI Hiroshi Niigata University, 医歯学系, 教授 (60242400)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 蛋白尿 / 糸球体上皮細胞 / スリット膜 / アンジオテンシン / ポドプラニン / シナプス小胞 / Neurexin / Podoplanin / ARB

Research Abstract

The aim of this project was to identify the target molecules for establishment of a novel therapy for proteinuria. This study demonstrated that the stimulation to type II receptor of angiotensin II and the enhancement of the function of synaptic vesicle molecules have protective effects for slit diaphragm.

Research Products

• [Journal Article] Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys. (2011)
  • Author(s): Saito A, Miyauchi N, Hashimoto T, Karasawa T, Han GD, Kayaba M, Sumi T, Tomita M, Ikezumi Y, Suzuki K, Koitabashi Y, Shimizu F, Kawachi H.
  • Journal Title: Am J Physiol Regul Integr Comp.Physiol 300
  • Peer Reviewed
• [Journal Article] Analysis of intestinal fibrosis in chronic colitis in mice induced by dextran sulfate sodium. (2011)
  • Author(s): Suzuki K, Sun X, Nagata M, Kawase T, Yamaguchi H, Sukumaran V, Kawauchi Y, Kawachi H, Nishino T, Watanabe K, Yoneyama H, Asakura H.
  • Journal Title: Pathol Int. 61 Pages: 228-238
  • NAID: 10031185076
  • Peer Reviewed
• [Journal Article] A notable case report of May-Hegglin anomaly with immune complex-related nephropathy : a genetic and histological analysis. (2011)
  • Author(s): Ohtsuka Y, Kanaji T, Nishi M, Sakai N, Sato T, Aoki S, Wakayama K, Nakazato S, Hisano S, Sado Y, Kawachi H, Izuhara K, Hamasaki Y.
  • Journal Title: Clin Nephrol. 75 Pages: 255-262
  • Peer Reviewed
• [Journal Article] Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy : potential role in mesangial matrix expansion. (2011)
  • Author(s): Ikezumi Y, Suzuki T, Karasawa T, Hasegawa H, Yamada T, Imai N, Narita I, Kawachi H, Polkinghorne KR, Nikolic-Paterson DJ, Uchiyama M.
  • Journal Title: Histopathology. 58 Pages: 198-210
  • Peer Reviewed
• [Journal Article] CD28 superagonist-induced regulatory T cell expansion ameliorates mesangioproliferative glomerulonephritis in rats. (2011)
  • Author(s): Miyasato K, Takabatake Y, Kaimori J, Kimura T, Kitamura H, Kawachi H, Li XK, Hunig T, Takahara S, Rakugi H, Isaka Y.
  • Journal Title: Clin Exp Nephrol. 15 Pages: 50-57
  • NAID: 10029004414
  • Peer Reviewed
• [Journal Article] Neurexin-1, apresynaptic adhesion molecule, localizes at the slit diaphragm ofthe glomerular podocytes in kidneys. (2011)
  • Author(s): Saito A
  • Journal Title: Am J Physiol Regul lntegr Comp Physiol Volume: 300
  • Peer Reviewed
• [Journal Article] Analysis of intestinal fibrosis in chronic colitis in mice induced by dextransulfate sodium. (2011)
  • Author(s): Suzuki K
  • Journal Title: Pathol Int Volume: 61 Pages: 228-238
  • Peer Reviewed
• [Journal Article] A notable case report of May-Hegglin anomaly with immunecomplex-related nephropathy (2011)
  • Author(s): Ohtsuka Y
  • Journal Title: Clin Nephrol Volume: 75 Pages: 255-262
  • Peer Reviewed
• [Journal Article] Identification of alternatively activated macrophages in new-onsetpaediatric and adult immunoglobulin A nephropathy : potential role inmesangial matrix expansion. (2011)
  • Author(s): Ikezumi Y
  • Journal Title: Histopathology Volume: 58 Pages: 198-210
  • Peer Reviewed
• [Journal Article] CD28 superagonist-induced regulatory T cell expansion amelioratesmesangioproliferative glomerulonephritis in rats. (2011)
  • Author(s): Miyasato K
  • Journal Title: Clin Exp Nephrol Volume: 15 Pages: 50-57
  • Peer Reviewed
• [Journal Article] Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome. (2010)
  • Author(s): Tanaka M, Asada M, Higashi AY, Nakamura J, Oguchi A, Tomita M, Yamada S, Asada N, Takase M, Okuda T, Kawachi H, Economides AN, Robertson E, Takahashi S, Sakurai T, Goldschmeding R, Muso E, Fukatsu A, Kita T, Yanagita M.
  • Journal Title: J Clin Invest.Mar 120 Pages: 768-777
  • NAID: 120001920754
  • Peer Reviewed
• [Journal Article] p21-activated kinases regulate actin remodeling in glomerular podocytes. (2010)
  • Author(s): Zhu J, Attias O, Aoudjit L, Jiang R, Kawachi H, Takano T.
  • Journal Title: Am J Physiol Renal Physiol. 298
  • Peer Reviewed
• [Journal Article] ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. (2010)
  • Author(s): Urushihara M, Takamatsu M, Shimizu M, Kondo S, Kinoshita Y, Suga K, Kitamura A, Matsuura S, Yoshizumi M, Tamaki T, Kawachi H, Kagami S.
  • Journal Title: Am J Physiol Renal Physiol. 298
  • Peer Reviewed
• [Journal Article] Effects of mineralocorticoid and angiotensin II receptor blockers on proteinuria and glomerular podocyte protein expression in a model of minimal change nephrotic syndrome. (2010)
  • Author(s): Fukuda A, Fujimoto S, Iwatsubo S, Kawachi H, Kitamura K.
  • Journal Title: Nephrology 15 Pages: 321-326
  • Peer Reviewed
• [Journal Article] Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase-1. (2010)
  • Author(s): Sun X, Suzuki K, Nagata M, Kawauchi Y, Yano M, Ohkoshi S, Matsuda Y, Kawachi H, Watanabe K, Asakura H, Aoyagi Y.
  • Journal Title: Pathol Int. 60 Pages: 93-101
  • Peer Reviewed
• [Journal Article] Contrasting effects of steroids and mizoribine on macrophage activation and glomerular lesions in rat thy-1 mesangial proliferative glomerulonephritis. (2010)
  • Author(s): Ikezumi Y, Suzuki T, Karasawa T, Hasegawa H, Kawachi H, Nikolic-Paterson DJ, Uchiyama M.
  • Journal Title: Am J Nephrol. 31 Pages: 273-282
  • Peer Reviewed
• [Journal Article] Racl contributes to actin organization in glomerular podocytes. (2010)
  • Author(s): Attias O, Jiang R, Aoudjit L, Kawachi H, Takano T.
  • Journal Title: Nephron Exp Nephrol. 114
  • Peer Reviewed
• [Journal Article] Effects of mineralocorticoid and angiotensin I I receptor blockers onproteinuria and glomerular podocyte protein expression in a model ofminimal change nephrotic syndrome. (2010)
  • Author(s): Fukuda A
  • Journal Title: Nephrology Volume: 15 Pages: 321-326
  • Peer Reviewed
• [Journal Article] Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase-1. (2010)
  • Author(s): Sun X
  • Journal Title: Pathol Int Volume: 60 Pages: 93-101
  • Peer Reviewed
• [Journal Article] Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome. (2010)
  • Author(s): Tanaka M
  • Journal Title: J Clin lnvest. 120 Pages: 768-777
  • Peer Reviewed
• [Journal Article] Contrasting effects of steroids and mizoribine on macrophage activation and glomerular lesions in rat thy-1 mesangial proliferative glomerulonephritis. (2010)
  • Author(s): Ikezumi Y
  • Journal Title: Am J Nephrol. 31 Pages: 273-282
  • Peer Reviewed
• [Journal Article] p21-activated kinases regulate actin remodeling in glomerular podocytes. (2010)
  • Author(s): Zhu J
  • Journal Title: AM J Physiol Renal Physiol. 298
  • Peer Reviewed
• [Journal Article] Therapeutic targets in the podocyte : findings in anti-slit diaphragm antibody-induced nephropathy. (2009)
  • Author(s): Kawachi H, Han GD, Miyauchi N, Hashimoto T, Suzuki K, Shimizu F.
  • Journal Title: J Nephrol. 22 Pages: 450-456
  • Peer Reviewed
• [Journal Article] Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats. (2009)
  • Author(s): Okada T, Sakaguchi T, Hatamura I, Saji F, Negi S, Otani H, Muragaki Y, Kawachi H., Shigematsu T.
  • Journal Title: Clin Exp Nephrol 13 Pages: 438-446
  • NAID: 10027226471
  • Peer Reviewed
• [Journal Article] Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats. (2009)
  • Author(s): Matsui I, Hamano T, Tomida K, Inoue K, Takabatake Y, Nagasawa Y, Kawada N, Ito T, Kawachi H, Rakugi H, Imai E, Isaka Y.
  • Journal Title: Nephrol Dial Transplant 24 Pages: 2354-2361
  • Peer Reviewed
• [Journal Article] Slit diaphragm dysfunction in proteinuric states : identification of novel therapeutic targets for nephrotic syndrome. (2009)
  • Author(s): Kawachi H, Suzuki K, Miyauchi N, Hashimoto T, Otaki Y, Shimizu F.
  • Journal Title: Clin Exp Nephrol. 13 Pages: 275-280
  • NAID: 10025586441
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blockade inhibits acute glomerular injuries with the alteration of receptor expression. (2009)
  • Author(s): Mii A, Shimizu A, Masuda Y, Ishizaki M, Kawachi H, Iino Y, Katayama Y, Fukuda Y.
  • Journal Title: Lab Invest. 89 Pages: 164-177
  • Peer Reviewed
• [Journal Article] Rac1 Contributes to actin organization in glomerular podocytes. (2009)
  • Author(s): Attias O
  • Journal Title: Nephron Exp Nephrol. 114
  • Peer Reviewed
• [Journal Article] ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. (2009)
  • Author(s): Urushihara M
  • Journal Title: AM J Physiol Renal Physiol. 298
  • Peer Reviewed
• [Journal Article] Therapeutic targets in the podocyte : findings in anti-slit diaphragm antibody-induced nephropathy. (2009)
  • Author(s): Kawashi H
  • Journal Title: J Nephrol. 22 Pages: 450-456
  • Peer Reviewed
• [Journal Article] Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats. (2009)
  • Author(s): Okada T
  • Journal Title: Clin Exp Nephrol. 13 Pages: 438-446
  • Peer Reviewed
• [Journal Article] Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats. (2009)
  • Author(s): Matsui I
  • Journal Title: Nephrol Dial Transplant (印刷中)
  • Peer Reviewed
• [Journal Article] Slit diaphragm dysfunction in proteinuric states : identification of novel therapeutic targets for nephrotic syndrome (2009)
  • Author(s): Kawachi H
  • Journal Title: Clin Exp Nephrol (印刷中)
  • NAID: 10025586441
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blockade inhibits acute glomerular injuries with the alteration of receptor expression (2009)
  • Author(s): Mii A
  • Journal Title: Lab Invest 89 Pages: 164-177
  • Peer Reviewed
• [Journal Article] The dissociation of NEPH1 from nephrin is involved in the development of rat model of focal segmental glomerulosclerosis. (2008)
  • Author(s): Otaki Y, Miyauchi N, Higa M, Takada A, Kuroda T, Gejyo F, Shimizu F, Kawachi H.
  • Journal Title: Am J Physiol Renal Physiol. 295
  • Peer Reviewed
• [Journal Article] Selective loss of podoplanin protein expression accompanies proteinuria and precedes alterations in podocyte morphology in a spontaneous proteinuric rat model. (2008)
  • Author(s): Koop K, Eikmans M, Wehland M, Baelde H, Ijpelaar D, Kreutz R,_Kawachi H, Kerjaschki D, de Heer E, Bruijn JA.
  • Journal Title: Am J Pathol 173 Pages: 315-326
  • Peer Reviewed
• [Journal Article] IFN-inducible protein 10 (CXCL10) regulates tubular cell proliferation in renal ischemia-reperfusion injury. (2008)
  • Author(s): Furuichi K, Wada T, Kitajikma S, Toyama T, Okumura T, Hara A, Kawachi H, Shimizu F, Sugaya T, Mukaida N, Narumi S, Matsushima K, Kaneko S.
  • Journal Title: Nephron Exp Nephrol. 109
  • Peer Reviewed
• [Journal Article] The mTOR inhibitor everolimus attenuates the time course of chronic anti-Thy1 nephritis in the rat. (2008)
  • Author(s): Wittmann S, Daniel C, Braun A, Vogelbacher R, Shimizu F, Kawachi H, Hugo C.
  • Journal Title: Nephron Exp Nephrol. 108
  • Peer Reviewed
• [Journal Article] Decreased tyrosine phosphorylation of nephrin in rat and human nephrosis. (2008)
  • Author(s): Uchida K, Suzuki K, Iwamoto M, Kawachi H, Ohno M, Horita S, Nitta K.
  • Journal Title: Kidney Int. 73 Pages: 926-932
  • Peer Reviewed
• [Journal Article] Rosuvastatin is additive to high-dose candesartan in slowing progression of experimental mesangioproliferative. (2008)
  • Author(s): Kramer S, Kron S, Wang-Rosenke Y, Loof T, Khadzhynov D, Morgera S, Kawachi H, Shimizu F, Martini S, Neumayer HH, Peters H.
  • Journal Title: Am J Physiol Renal Physiol. 294
  • Peer Reviewed
• [Journal Article] Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat. (2008)
  • Author(s): Kramer S, Wang-Rosenke Y, Scholl V, Binder E, Loof T, Khadzhynov D, Kawachi H, Shimizu F, Diekmann F, Budde K, Neumayer HH, Peters H.
  • Journal Title: Am J Physiol Renal Physiol. 294
  • Peer Reviewed
• [Journal Article] Eplerenone potentiates the antiproteinuric effects of enalapril in experimental nephrotic syndrome. (2008)
  • Author(s): Nakhoul F, Khankin E, Yaccob A, Kawachi H, Karram T, Awaad H, Nakhoul N, Hoffman A, Abassi Z.
  • Journal Title: Am J Physiol Renal Physiol. 294
  • Peer Reviewed
• [Journal Article] Nephrin mediates actin reorganization via phosphoinositide 3-kinase in podocytes. (2008)
  • Author(s): Zhu J, Sun N, Aoudjit L, Li H, Kawachi H, Lemay S, Takano T.
  • Journal Title: Kidney Int. 73 Pages: 556-566
  • Peer Reviewed
• [Journal Article] Use of mizoribine as a rescue drug for steroid-resistant pediatric IgA nephropathy. (2008)
  • Author(s): Ikezumi Y, Suzuki T, Karasawa T, Kawachi H, Nikolic-Paterson DJ, Uchiyama M.
  • Journal Title: Pediatr Nephrol 23 Pages: 645-650
  • Peer Reviewed
• [Journal Article] Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases. (2008)
  • Author(s): Ikezumi Y
  • Journal Title: Biochem Biophys Res Commun 28 : 376 Pages: 706-711
  • Peer Reviewed
• [Journal Article] Dissociation of NEPH1 from nephrin is involved in development of a rat model of focal segmental glomerulosclerosis. (2008)
  • Author(s): Otaki Y
  • Journal Title: Am J Physiol Renal physiol 295 Pages: 1376-1387
  • Peer Reviewed
• [Journal Article] Selective loss of podoplanin protein expression accompanies proteinuria and precedes alterations in podocyte morphology in a spontaneous proteinuric rat model. (2008)
  • Author(s): Koop K
  • Journal Title: Am J Physiol 173 Pages: 315-326
  • Peer Reviewed
• [Journal Article] IFN-inducible protein 10(CXCL1O)regulates tubular cell proliferation in renal ischemia-reperfusion injury. (2008)
  • Author(s): Furuichi K
  • Journal Title: Nephron Exp Nephrol 109 Pages: 29-38
  • Peer Reviewed
• [Journal Article] Suppressive activity of pemirolast potassium, an antiallergic drug, on glomerulonephritis. Studies in glomerulonephritis model rats and in patients with chronic glomerulonephritis concurrently affected by allergic rhinitis. (2008)
  • Author(s): Gohda T
  • Journal Title: Arzneimittelforschung 58 Pages: 18-23
  • Peer Reviewed
• [Journal Article] The mTOR inhibitor everolimus attenuates the time course of chronic anti-Thy1 nephritis in the rat. (2008)
  • Author(s): Wittmann S
  • Journal Title: Nephron Exp Nephrol 108 Pages: 45-56
  • Peer Reviewed
• [Journal Article] Decreased tyrosine phosphorylation of nephrin in rat and human nephrosis. (2008)
  • Author(s): Uchida K
  • Journal Title: Kidney Int 73 Pages: 926-932
  • Peer Reviewed
• [Journal Article] Rosuvastatin is additive to high-dose candesartan in slowing progression of experimental mesangioproliferative glomerulosclerosis. (2008)
  • Author(s): Kramer S
  • Journal Title: Am J Physiol Renal physiol 294 Pages: 801-811
  • Peer Reviewed
• [Journal Article] Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1-induced chronic glomerulosclerosis of the rat. (2008)
  • Author(s): Kramer S
  • Journal Title: Am J Physiol Renal physiol 294 Pages: 440-449
  • Peer Reviewed
• [Journal Article] Eplerenone potentiates the antiproteinuric effects of enala pril in experimental nephrotic syndrome. (2008)
  • Author(s): Nakhoul F
  • Journal Title: Am J Physiol Renal physiol 294 Pages: 628-637
  • Peer Reviewed
• [Presentation] Calcineurin is involved in the development of proteinuria in an experimental model of MCNS. (2010)
  • Author(s): Tomita M
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国デンバー
  • Year and Date: 2010-11-19
• [Presentation] Calcineurin is involved in the development of proteinuria in an experimental model of MCNS. (2010)
  • Author(s): Tomita M
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国 デンバー
  • Year and Date: 2010-11-19
• [Presentation] Expression of Podoplanin in MCNS : Urinary podoplanin is a Novel Marker to Predict Podocyte Injury. (2009)
  • Author(s): Suzuki K
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国サンディエゴ
  • Year and Date: 2009-10-31
• [Presentation] Expression of Podoplanin in MCNS : Urinary podoplaninin is a Novel Marker to Predict Podocyte Injury (2009)
  • Author(s): Suzuki K
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国サンディエゴ
  • Year and Date: 2009-10-31
• [Presentation] Podoplanin was expressed on both apical and basal surfaces of podocyte, and the basal podoplanin plays a role in maintenance of not only the foot process structure but also the barrier function of glomerular capillary wall. (2008)
  • Author(s): Suzuki K
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国フィラデルフィア
  • Year and Date: 2008-11-06
• [Presentation] An Adhesion Molecule Ninjurin-II Is Expressed in the Podocyte and Its Expression Is Altered in Podocyte with Slit Diaphragm Dysfunction (2008)
  • Author(s): Han GD
  • Organizer: 米国腎臓学会
  • Place of Presentation: 米国フィラデルフィア
  • Year and Date: 2008-11-06
• [Book] 専門医のための腎臓病学 (2009)
  • Author(s): 河内裕
  • Publisher: 医学書院
• [Book] 専門医のための腎臓病学 (2009)
  • Author(s): 河内 裕
  • Publisher: 医学書院(印刷中)
• [Remarks] 河内裕:糸球体上皮細胞の新しい機能分子-蛋白尿の新規治療法開発のためのターゲット分子の探索-第31回腎臓セミナー、2009、東京
• [Remarks] 河内裕:ポドサイト研究の最前線-臨床応用に向けての展望-第1回Front J、2009、東京
• [Remarks] 河内裕:スリット膜関連分子-最近の知見-第93回東京腎生理集談会、2008、東京
• [Remarks] ホームページ
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