Screening of novel biomarkers and therapeutic targets in diabetic nephropathy

• Project/Area Number: 19590949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: SUGAHARA Akira Kyoto University, 医学研究科, 臨床教授 (00312223)
• Co-Investigator(Renkei-kenkyūsha): MORI Kiyoshi 京都大学, 医学研究科, 講師 (60343232) ; SATOU Noriko 京都医療センター・臨床研究センター, 研究員 (80373512)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 腎臓学 / 内科 / マイクロアレイ / 糖尿病 / 蛋白質 / 慢性腎不全 / 慢性腎臓病 / バイオマーカー / ネフロン / 探索

Research Abstract

1型および2型糖尿病のマウスモデルを用いて、糖尿病性腎症の早期に発現増加が改善する遺伝子としてgremlin 1、growth arrest-specific 6、Wt-1、Rab3bなどを同定し、これらの因子の糖尿病性腎症への関与が示唆された。さらに糖尿病性腎症においては尿中Ngal が増加し、アンギオテンシン受容体阻害薬の投与により減少することを明らかにし、尿中Ngal の新規バイオマーカーとしての有用性を報告した。

Research Products

• [Journal Article] Reduction of urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blocker in hypertensive patients (2009)
  • Author(s): Kasahara M, Mori K, Satoh N, Kuwabara T, Yokoi H, Shimatsu A, Sugawara A, Mukoyama M, Nakao K
  • Journal Title: Nephrol Dial Transpl (in press)
  • Peer Reviewed
• [Journal Article] Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons (2009)
  • Author(s): Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Yoshioka T, Ogawa Y, Imamaki H, Kusakabe T, Ebihara K, Omata M, Satoh N, Sugawara A, Barasch J, Nakao K
  • Journal Title: Kidney Int 75(3) Pages: 285-94
  • NAID: 120005678177
  • Peer Reviewed
• [Journal Article] Reduction of urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blocker in hypertensive patients. (2009)
  • Author(s): M. Kasahara, et al.
  • Journal Title: Nephrol Dial Transplant (印刷中)
  • Peer Reviewed
• [Journal Article] Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. (2009)
  • Author(s): T. Kuwabara, et al.
  • Journal Title: Kidney Int 75 Pages: 285-294
  • Peer Reviewed
• [Journal Article] Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury (2008)
  • Author(s): Nickolas TL, O'Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J
  • Journal Title: Ann Intern Med 148(11) Pages: 810-9
  • Peer Reviewed
• [Journal Article] Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis (2008)
  • Author(s): Nagae T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Suganami T, Sawai K, Yoshioka T, Koshikawa M, Saito Y, Ogawa Y, Kuwabara T, Tanaka I, Sugawara A, Kuwahara T, Nakao K
  • Journal Title: Kidney Int 74(1) Pages: 70-80
  • Peer Reviewed
• [Journal Article] Overexpression of connective tissue growth factor in podocytes worsens diabetic nephropathy in mice (2008)
  • Author(s): Yokoi H, Mukoyama M, Mori K, Kasahara M, Suganami T, Sawai K, Yoshioka T, Saito Y, Ogawa Y, Kuwabara T, Sugawara A, Nakao K
  • Journal Title: Kidney Int 73(4) Pages: 446-55
  • Peer Reviewed
• [Journal Article] Myasthenia-like syndrome induced by cibenzoline overdose in a patient with chronic kidney disease (2008)
  • Author(s): Kawasaki H, Yahata K, Okamoto C, Imamaki H, Seta K, Sugawara A
  • Journal Title: Nippon Jinzo Gakkai Shi 50(7) Pages: 942-7
  • NAID: 10024901318
  • Peer Reviewed
• [Journal Article] Systemic AA amyloidosis caused by familial Mediterranean fever and response to colchicines (2008)
  • Author(s): Fukui N, Mukoyama M, Saito Y, Mori K, Kasahara M, Yokoi H, Ogawa Y, Kuwabara T, Sugawara A, Nakao K.
  • Journal Title: Nippon Naika Gakkai Zasshi 97(12) Pages: 3046-8
  • NAID: 10024933107
  • Peer Reviewed
• [Journal Article] Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis. (2008)
  • Author(s): T. Nagae, et al.
  • Journal Title: Kidney Int 74 Pages: 70-80
  • Peer Reviewed
• [Journal Article] Overexpression of connective tissue growth factor in podocytes worsens diabetic nephropathy in mice. (2008)
  • Author(s): H. Yokoi, et al.
  • Journal Title: Kidney Int 73 Pages: 446-455
  • Peer Reviewed
• [Journal Article] Myasthenia-like syndrome induced by cibenzoline overdose in a patient with chronic kidney disease. (2008)
  • Author(s): H. Kawasaki, et al.
  • Journal Title: Nippon Jinzo Gakkai Shi 50 Pages: 942-947
  • Peer Reviewed
• [Journal Article] Systemic AA amyloidosis caused by familial Mediterranean fever and response to colchicine. (2008)
  • Author(s): N. Fukui, et al.
  • Journal Title: Nippon Jinzo Gakkai Shi 97 Pages: 3046-3048
  • Peer Reviewed
• [Journal Article] Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase (2008)
  • Author(s): Nagae T, Mori K, et. al.
  • Journal Title: Kidney Int (掲載決定)
  • Peer Reviewed
• [Journal Article] Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage (2007)
  • Author(s): Mori K, Nakao K
  • Journal Title: Kidney Int 71(10) Pages: 967-70
  • NAID: 120004225591
  • Peer Reviewed
• [Journal Article] Expression of CCN1 (CYR61) in developing, normal, and diseased human kidney (2007)
  • Author(s): Sawai K, Mukoyama M, Mori K, Kasahara M, Koshikawa M, Yokoi H, Yoshioka T, Ogawa Y, Sugawara A, Nishiyama H, Yamada S, Kuwahara T, Saleem MA, Shiota K, Ogawa O, Miyazato M, Kangawa K, Nakao K
  • Journal Title: Am J Physiol Renal Physiol 293(4) Pages: 1363-72
  • Peer Reviewed
• [Journal Article] Overexpression of connective tissue growth factor in podocytes worsens diabetic nephropathy in mice. (2007)
  • Author(s): Yokoi H, Mukoyama M, et. al.
  • Journal Title: Kidney Int 73 Pages: 446-455
  • Peer Reviewed
• [Journal Article] Expression of CCN1 (CYR61) in developing, normal, and diseased human kidney. (2007)
  • Author(s): Sawai K, Mukoyama M, et. al.
  • Journal Title: Am J Physiol Renal Physiol 293
  • Peer Reviewed
• [Journal Article] Altered gene expression related to glomerulogenesis and podocyte structure in early diabetic nephropathy of db/db mice and its restoration by pioglitazone (2006)
  • Author(s): Makino H, Miyamoto Y, Sawai K, Mori K,Mukoyama M, Nakao K, Yoshimasa Y, Suga S
  • Journal Title: Diabetes 55(10) Pages: 2747-56
  • Peer Reviewed
• [Presentation] Urinary Neutrophil Gelatinase-Associated Lipocalin (Ngal) is a Powerful Bioraarker of Disease Activity and Treatment Efficacy in Chronic Kidney Disease (CKD) (2009)
  • Author(s): T. Kuwabara, et al.
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-22
• [Presentation] Urinary Neutrophil Gelatinase-Associated Lipocalin(Ngal)is a Powerful Biomarker of Disease Activity and Treatment Efficacy in Chronic Kidney Disease(CKD) (2009)
  • Author(s): Kuwabara T, Mori K, Mukoyama M, Sugawara A, Nakao K
  • Organizer: 日本循環器学会学術集
  • Place of Presentation: 大阪
• [Presentation] Reduction of urinary excretion of neutrophil gelatinase associated lipocalin (Ngal) by angiotensin receptor (2008)
  • Author(s): T. Kuwabara, et al.
  • Organizer: American Society of Nephrology (ASN)
  • Place of Presentation: Philadelphia
  • Year and Date: 2008-11-08
• [Presentation] 高血圧・高脂血症を伴うCKD(慢性腎臓病)患者における血圧コントロール後のスタテンによる蛋白尿減少、腎保護効果について (2008)
  • Author(s): 岡本千夏, ほか
  • Organizer: 日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-09
• [Presentation] Urinary Ngal is a kidney injury biomarker which integrates information of damage in glomeruli, proximal tubules and distal nephrons. (2008)
  • Author(s): K. Mori, et al.
  • Organizer: International Society of Hypertension (ISH)
  • Place of Presentation: Berlin
  • Year and Date: 2008-06-19
• [Presentation] Adrenomedullin gene transfer in rat kidney inhibits connective tissue growth factor, extracellular signal-regulated kinase, and renal fibrosis. (2008)
  • Author(s): T. Nagae, et al.
  • Organizer: The Endocrine Society (ENDO)
  • Place of Presentation: San Francisco
  • Year and Date: 2008-06-15
• [Presentation] 尿中Ngal濃度の解析から考えられる理想の腎障害マーカー像(Kidney Biomarkerology 2008). (2008)
  • Author(s): 森潔, ほか
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-30
• [Presentation] ネフローゼ治療中の血中・尿中Neutrophil gelatinase associated lipocalin (Ngal)濃度の推移 (2008)
  • Author(s): 桑原孝成, ほか
  • Organizer: 日本内科学会講演会
  • Place of Presentation: 東京
  • Year and Date: 2008-04-12
• [Presentation] Urinary Ngal is a kidney injury biomarker which integrates information of damage in glomeruli, proximal tubules and distal nephrons (2008)
  • Author(s): Mori K, Kuwabara T, Mukoyama M, Kasahara M, Yokoi H, Ogawa Y, Saito Y, Imamaki H, Sugawara A, Barasch J, Nakao
  • Organizer: International Society of Hypertension (ISH) meeting
  • Place of Presentation: Berlin
• [Presentation] Adrenomedullin gene transfer into rat kidney ameliorates obstructive renal fibrosis through inhibition of connective tissue growth factor and extracellular signal-regulated kinase (2008)
  • Author(s): Nagae T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Suganami T, Sawai K, Yoshioka T, Koshikawa M, Saito Y, Ogawa Y, Kuwabara T, Tanaka I, Sugawara A, Kuwahara T, Nakao K
  • Organizer: International Society of Hypertension(ISH)meeting
  • Place of Presentation: Berlin
• [Presentation] Urinary Ngal as an early biomarker for diabetic nephropathy in mice (2008)
  • Author(s): Mori K, Kuwabara T, Mukoyama M, Saito Y, Kasahara M, Yokoi H, Ogawa Y, Imamaki H, Nakao K
  • Organizer: The Shiga International Symposium on Diabetic Nephropathy meeting
  • Place of Presentation: Otsu
• [Presentation] Reduction of urinary excretion of neutrophil gelatinaseassociated lipocalin(Ngal)by angiotensin receptor blockers(ARBs)in diabetic or obese subjects (2008)
  • Author(s): Kuwabara T, Mori K, Satoh N, Kasahara M, Yokoi H, Saito Y, Imamaki H, Nagae T, Ogawa Y, Barasch J, Sugawara A, Mukoyama M, Nakao K
  • Organizer: American Society of Nephrology(ASN)meeting
  • Place of Presentation: Philadelphia
• [Presentation] 1型及び2型糖尿病に伴う糖尿病性腎症モデルマウスの糸球体における遺伝子発現変動パターンの網羅的解析 (2008)
  • Author(s): 森潔、〓原孝成、向山政志、斎藤陽子、笠原正登、横井秀基、吉岡徹朗、小川喜久、今牧博貴、菅原照、中尾一和
  • Organizer: 日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] ネフローゼ治療中の血中・尿中Neutrophil gelatinase-associated lipocalin (Ngal)濃度の推移 (2008)
  • Author(s): 〓原孝成, 森潔, 向山政志, 笠原正登,横井秀基, 小川喜久, 齋藤陽子, 今牧博貴, 菅原照, 中尾一和
  • Organizer: 日本内科学会講演会
  • Place of Presentation: 東京
• [Presentation] 尿中Ngal 濃度の解析から考えられる理想の腎障害マーカー像(Kidney Biomarkerology 2008) (2008)
  • Author(s): 森潔、向山政志、笠原正登、横井秀基、〓原孝成、中尾一和
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 福岡
• [Presentation] 糖尿病性腎症モデルマウスの回復早期に発現変動する遺伝子群の同定 (2008)
  • Author(s): 森潔、〓原孝成、向山政志、斎藤陽子、笠原正登、横井秀基、小川喜久、今牧博貴、菅原照、中尾一和
  • Organizer: 日本内分泌学会学術総会
  • Place of Presentation: 青森
• [Presentation] 内分泌因子・液性因子と腎予後予測-NgalとBNPを中心に- (2008)
  • Author(s): 向山政志、森潔、笠原正登、原田昌樹、中尾一和
  • Organizer: 日本腎臓学会西部学術大会
  • Place of Presentation: 名古屋
• [Presentation] 2種の糖尿病性腎症モデルマウスの糸球体において共通に発現増加する遺伝子の網羅的解析 (2008)
  • Author(s): 森潔、〓原孝成、向山政志、笠原正登、横井秀基、斎藤陽子、小川喜久、今牧博貴、菅原照、中尾一和
  • Organizer: 日本糖尿病合併症学会
  • Place of Presentation: 東京
• [Presentation] 高血圧・高脂血症を伴うCKD(慢性腎臓病)患者における血圧コントロール後のスタチンによる蛋白尿減少、腎保護効果について (2008)
  • Author(s): 岡本千夏、小泉三輝、菊地祐子、瀬田公一、八幡兼成、菅原照
  • Organizer: 日本高血圧学会総会
  • Place of Presentation: 札幌
• [Presentation] Forest Fire Theory for Renal Failure and Clinical Impact of Neutrophil Gelatinase-Associated Lipocalin (2007)
  • Author(s): Mori K, Mukoyama M, Nickolas TL, Barasch J, Nakao K
  • Organizer: International Society of Nephrology(ISN)meeting
  • Place of Presentation: Brazil
• [Presentation] Distinct Urinary Excretion of Albumin, Beta-2 microglobulin and Neutrophil Gelatinase-Associated Lipocalin in Mouse Models of Diabetic Nephropathy (2007)
  • Author(s): Kuwabara T, Mori K, Mukoyama M, Saito Y, Kasahara M, Yokoi H, Yoshioka T, Ogawa Y, Imamaki H, Sugawara A, Barasch J, Nakao K
  • Organizer: American Society of Nephrology(ASN)meeting
  • Place of Presentation: San Francisco
• [Presentation] Blood and Urinary Neutrophil Gelatinase-Associated Lipocalin (Ngal) Levels in the Treatment Courses of Proteinuric Glomerular Diseases (2007)
  • Author(s): Mori K, Kuwabara T, Mukoyama T, Kasahara M, Yokoi H, Yoshioka T, Ogawa Y, Saito Y, Imamaki H, Sugawara A, Barasch J, Nakao K
  • Organizer: American Society of Nephrology(ASN)meeting
  • Place of Presentation: San Francisco
• [Presentation] 夜間血圧コントロールによる蛋白尿減少と腎保護効果 (2007)
  • Author(s): 岡本千夏、小泉三輝、菊地祐子、瀬田公一、八幡兼成、菅原照.
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 浜松
• [Presentation] 腎不全の「山火事」理論とNeutrophil gelatinase-associated lipocalin (2007)
  • Author(s): 森潔、向山政志、笠原正登、横井秀基、〓原孝成、吉岡徹朗、小川喜久、齊藤陽子、菅原照、中尾一和
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 浜松
• [Presentation] I型及びII型糖尿病に伴う糖尿病性腎症モデルマウスの糸球体における遺伝子発現変動パターンの網羅的解析 (2007)
  • Author(s): 〓原孝成、森潔、向山政志、齊藤陽子、笠原正登、横井秀基、吉岡徹朗、小川喜久、菅原照、中尾一和
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 浜松
• [Presentation] Neutrophil gelatinaseassociated lipocalinの臨床的意義及び腎不全の「山火事」理論 (2007)
  • Author(s): 森潔、向山政志、笠原正登、横井秀基、〓原孝成、吉岡徹朗、小川喜久、齊藤陽子、菅原照、中尾一和
  • Organizer: 日本透析医学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 腎不全におけるNgal : siderophore : Fe複合体の意義 (2007)
  • Author(s): 森潔、向山政志、笠原正登、中尾一和
  • Organizer: 日本透析医学会学術集会
  • Place of Presentation: 大阪
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/kidney.html