The mechanism of nephron number reduction induced by intrauterine fetal growth retardation

• Project/Area Number: 18591225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Keio University
• Principal Investigator: HIDA Mariko Keio University, 医学部, 共同研究員 (20276306)
• Co-Investigator(Kenkyū-buntansha): AWAZU Midori 慶應義塾大学, 医学部, 講師 (20129315)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,350,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 子宮内発育不全 / 腎臓発生 / oligomeganephronia / レプチン / MAP キナーゼ / MAPキナーゼ / 矮小腎 / 生活習慣病

Research Abstract

本研究は子宮内胎児発育遅滞(IUGR)や低出生体重(LBW)の成人期高血圧発症の原因である腎のネフロン(尿を作る装置)数減少、腎容積の減少の発生機序についての検討である。培養細胞において、IUGR児で血中濃度が低下するホルモン(レプチン)が、腎発生に必須である細胞内信号伝達因子MAPキナーゼを介し、細胞の成長・遊走・分化を刺激することが示された。レプチン欠乏がMAPキナーゼを介しIUGR、LBWの腎発生異常に関与する可能性が示唆された。

Research Products

• [Journal Article] Efficacy and safety of lisinopril for mild childhood IgA nephropathy : a pilot study (2009)
  • Author(s): Nakanishi K, Iijima K, Ishikura K, Hataya H, Awazu M et.al.
  • Journal Title: Japanese Pediatric IgA Nephropathy Treatment Study Group. Pediatr Nephrol 24 Pages: 845-849
  • Peer Reviewed
• [Journal Article] Tubulointerstitial nephritis and uveitis syndrome : a case with an autoimmune reactivity against retinal and renal antigens (2008)
  • Author(s): Shimazaki K, Jirawuthiworavong GV, Nguyen EV, Awazu M, Levinson RD, Gordon LK
  • Journal Title: Ocul Immunol Inflamm 16(1) Pages: 51-53
  • Peer Reviewed
• [Journal Article] Activated extracellular signalregulated kinase correlates with cyst formation and transforming growth factor-beta expression in fetal obstructive uropathy (2008)
  • Author(s): Omori S, Kitagawa H, Koike J, Fujita H, Hida M, Pringle KC, Awazu M.
  • Journal Title: Kidney Int. 73(9) Pages: 1031-1037
  • Peer Reviewed
• [Journal Article] Chronic kidney disease に対するangiotensin-converting enzyme inhibitorとangiotensin receptor blockerの腎保護作用 (2008)
  • Author(s): 藤田直也, 山田拓司, 上村治, 秋岡祐子, 粟津緑, 他
  • Journal Title: 日本小児臨床薬理学会雑誌 21 Pages: 134-137
  • Peer Reviewed
• [Journal Article] 【小児疾患診療のための病態生理】腎・泌尿器疾患腎尿路奇形 (2008)
  • Author(s): 粟津緑
  • Journal Title: 小児内科 40 Pages: 881-886
• [Journal Article] 腎疾患の病態生理 腎腫大のメカニズム編異形成腎の腎腫大 (2008)
  • Author(s): 粟津緑
  • Journal Title: 腎と透析 65 Pages: 819-823
• [Journal Article] 後腎間葉細胞の増殖、E カドヘリン発現、MAPキナーゼ活性に対するBMP7の濃度依存性効果 (2008)
  • Author(s): 粟津緑, 大森さゆ, 長田道夫, 飛彈麻里子
  • Journal Title: 発達腎研究会誌 16 Pages: 39-42
  • Peer Reviewed
• [Journal Article] Efficacy and safety of lisinopril for mild childhood IgA nepnropathy : a pilot study. (2008)
  • Author(s): Nakanishi K, et al.
  • Journal Title: Pediatr Nephrol. 24(4) Pages: 845-849
• [Journal Article] Activated extracellular signal-regulated kinase correlates with eyst formation and transforminggrowth factor-beta expression in fetal obstructive uropathy. (2008)
  • Author(s): Omori S, et al.
  • Journal Title: Kidney Int. 73(9) Pages: 1031-1037
• [Journal Article] 【小児腎疾患の診断・治療戦略】保護者、園・学校関係者へのアドバイス 腎疾患患者の食事 (2008)
  • Author(s): 杉井杏子, 粟津緑
  • Journal Title: 小児内科 41・2 Pages: 228-230
• [Journal Article] 【小児疾患診療のための病態生理】腎・泌尿器疾患 腎尿路奇形 (2008)
  • Author(s): 粟津緑
  • Journal Title: 小児内科 40・増刊 Pages: 881-886
• [Journal Article] 腎疾患の病態生理 腎腫大のメカニズム編 異形成腎の腎腫大 (2008)
  • Author(s): 粟津緑
  • Journal Title: 腎と透析 65・6 Pages: 819-823
• [Journal Article] 後腎間葉細胞の増殖、Eカドヘリン発現、MAPキナーセ活性に対するBMP7の濃度依存性効果 (2008)
  • Author(s): 粟津緑
  • Journal Title: 発達腎研究会誌 16・1 Pages: 39-42
• [Journal Article] Activated extracellular signal-regulated kinase correlates with cyst formation and ransforming growth factor-b expression in fetal obstructive uropath (2008)
  • Author(s): Omori S, et. al.
  • Journal Title: Kidney International 16 Pages: 51-53
  • Peer Reviewed
• [Journal Article] Tubulointerstitial nephritis and uveitis syndrome:a case with an autoimmune reactivity against retinal and renal antigens (2008)
  • Author(s): Shimazaki K, et. al.
  • Journal Title: Ocul Immunol Inflamm 16 Pages: 51-53
  • Peer Reviewed
• [Journal Article] 【これだけは知っておきたい分子腎臓学2007】 MAP kinase(ERK) (2007)
  • Author(s): 粟津緑
  • Journal Title: 腎と透析 63 Pages: 554-556
• [Journal Article] 【腎・泌尿器疾患診療マニュアル小児から成人まで】尿細管機能異常症nephrogenic syndrome of inappropriate antidiuresis (2007)
  • Author(s): 粟津緑
  • Journal Title: 日本医師会雑誌 136巻特別2
• [Journal Article] 尿細管上皮細胞分化・形質維持におけるJNKの役割 (2007)
  • Author(s): 藤田尚代(平塚共済病院小児科), 大森さゆ, 飛彈麻里子, 粟津緑
  • Journal Title: 発達腎研究会誌 15 Pages: 8-13
  • Peer Reviewed
• [Journal Article] 尿細管上皮細胞分化・形質維持におけるJNKの役割 (2007)
  • Author(s): 藤田尚代 他
  • Journal Title: 発達腎研究会誌 15(印刷中)
• [Journal Article] Steroid treatment for severe childhood IgA nephropathy : a randomized, controlled trial (2006)
  • Author(s): Yoshikawa N, Honda M, Iijima K, Awazu M et.al.
  • Journal Title: Japanese Pediatric IgA Nephropathy Treatment Study Group. Clin J Am Soc Nephrol 1(3) Pages: 511-517
  • Peer Reviewed
• [Journal Article] Hyponatremia, hypophosphatemia, and hypouricemia in a girl with macrophage activation syndrome (2006)
  • Author(s): Yamazawa K, Kodo K,Maeda J, Omori S, Hida M, Mori T, Awazu M.
  • Journal Title: Pediatrics 118 Pages: 2557-2560
  • Peer Reviewed
• [Journal Article] Extracellular signal-regulated kinase inhibition slows disease progression in mice with polycystic kidney disease (2006)
  • Author(s): Omori S, Hida M, Fujita H, Takahashi H, Tanimura S, Kohno M, Awazu M
  • Journal Title: J Am Soc Nephrol 17(6) Pages: 1604-1614
  • Peer Reviewed
• [Journal Article] ERK阻害によるマウス多発性嚢胞腎進展抑制 (2006)
  • Author(s): 粟津緑, 藤田尚代, 飛彈麻里子, 他
  • Journal Title: 発達腎研究会誌 14 Pages: 49-53
  • Peer Reviewed
• [Journal Article] 腎発生におけるMAPキナーゼ (2006)
  • Author(s): 粟津緑
  • Journal Title: 日本小児科学会雑誌 110 Pages: 647-655
  • NAID: 10024461237
  • Peer Reviewed
• [Journal Article] 【超低出生体重児の生存限界と成育限界】長期予後からみた成育限界血圧, 腎機能から (2006)
  • Author(s): 粟津緑, 飛彈麻里子
  • Journal Title: 小児科 46 Pages: 2113-2121
• [Journal Article] Leptin induces hypertrophy via mitogen-activated protein kinase pathways in a metanephric mesenchymal cell line. (2006)
  • Author(s): Hida, M. et al.
  • Journal Title: J. Am. Soc. Nephrol. 17
• [Journal Article] Dose-dependent effects of BMP7 on proliferation. E-cadherin expression, and MAP kinase activation in a meranephric mesenchymal cell line. (2006)
  • Author(s): Awazu.M.et al.
  • Journal Title: J. Am. Soc. Nephrol. 17
• [Journal Article] ヒツジ胎仔尿路閉塞モデルにおける胎生期シャントのERK活性化、TGF-β発現への影響 (2006)
  • Author(s): 大森さゆ 他
  • Journal Title: 日腎会誌 48 Pages: 216-216
• [Journal Article] Dysreguration of mitogen-activated proteir kinases in murine polycystic kidney disease. (2006)
  • Author(s): Omori, S. et al.
  • Journal Title: J Am Soc Nephrol 17 Pages: 1604-1614
• [Journal Article] Hyponatremia, hypophosphatemia, and hypouricemia in a girl with macrophage activation syndrome. (2006)
  • Author(s): Yamazawa, N. et al.
  • Journal Title: Pediatrics 118 Pages: 2557-2560
• [Journal Article] ERK阻害によるマウス多発性嚢胞腎進展抑制 (2006)
  • Author(s): 粟津緑 他
  • Journal Title: 発達腎研究会誌 14 Pages: 49-53
• [Presentation] Leptin Induces Migration Via ERK and p38 in a Me tanephric Mesenchymal Cell Line (2008)
  • Author(s): Hida M, Awazu M
  • Organizer: T he American Society of Nephrology Renal Week 2008
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-06
• [Presentation] Maternal Nutr ient Restriction Activates Developm entally Regulated Signaling Pathway s in Fetal Rat Kidney (2008)
  • Author(s): Awazu M, Hida M.
  • Organizer: The American Society of Nephrology Renal Week 2008
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-06
• [Presentation] Leptin Induces Migration Via ERK and p38 in a Metanephric Mesenchymal Cell Line (2008)
  • Author(s): Hida M, Awazu M
  • Organizer: Renal Week (Annual Meeting) 2008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] Maternal Nutrient Restriction Activates Developmentally Regulated Signaling Pathways in Fetal Rat Kidney (2008)
  • Author(s): Awazu M, Hida M
  • Organizer: Renal Week (Annual Meeting) 2008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] 学校検尿で蛋白尿を指摘され、軽度腎機能低下を確認した超低出生体重児二症例 (2008)
  • Author(s): 飛彈麻里子, 他
  • Organizer: 第53回日本未熟児新生児学会
  • Place of Presentation: 札幌
• [Presentation] Leptin induces migration and epithelialization in a metanephric mesenchymal cell line (2008)
  • Author(s): Hida M, Omori S, Nagata M, Awazu M.
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡
• [Presentation] マイクロアレイを用いた母体低栄養ラット胎仔腎における遺伝子発現解析 (2008)
  • Author(s): 粟津緑、飛彈麻里子
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡
• [Presentation] 腎発生におけるMAPキナーゼ研究を通してわかった発達腎臓学の魅力 (2008)
  • Author(s): 粟津緑
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡
• [Presentation] マイクロアレイを用いた母体低栄養ラット胎仔腎における遺伝子発現解析 (2008)
  • Author(s): 粟津緑、飛彈麻里子
  • Organizer: 第51回日本腎臓学会学術集会
  • Place of Presentation: 福岡
• [Presentation] 学校検尿で蛋白尿を指摘され、軽度腎機能低下を確認した超低出生体重児二症例 (2008)
  • Author(s): 飛彈麻里子, 他
  • Organizer: 第53回日本未熟児新生児学会
  • Place of Presentation: 札幌市
• [Presentation] Leptin induces migration and epithelialization in a met anephric mesenchyial cell Line. (2008)
  • Author(s): Hida M, Omori S, Nagata M, Awazu M
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡市
• [Presentation] マイクロアレイを用いた母体低栄養ラツト胎仔腎における遺伝子発現解析 (2008)
  • Author(s): 粟津緑, 飛彈麻里子
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡市
• [Presentation] 小児、青年期高血圧前症における自由行動下血圧測定 (2008)
  • Author(s): 藤田尚代, 松岡誠治, 粟津緑
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡市
• [Presentation] 腎発生におけるMAPキナーゼ・研究を通してわかった発達腎臓学の魅力 (2008)
  • Author(s): 粟津緑
  • Organizer: 第43回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡市
• [Presentation] Leptin induces hypertrophy of metanephric mesenchymal cells via mitogen-activa ted protein kinases (2007)
  • Author(s): Hida M, et. al.
  • Organizer: 3rd Asian Society of Pediatric Research
  • Place of Presentation: 東京
  • Year and Date: 2007-11-26
• [Presentation] Effect of mater nal dexamethasone treatment on fetal ki dney gene expression The American Soci ety of Nephrology Renal Week 2007 (2007)
  • Author(s): Hida M, Awazu M.
  • Place of Presentation: Sanflancisco, USA
  • Year and Date: 2007-11-02
• [Presentation] Effect of mater nal nutrient restriction on fetal kidne y gene expression (2007)
  • Author(s): Awazu M, Hida M.
  • Organizer: The American Society of Nephrology Renal Week 2007
  • Place of Presentation: Sanflancisco, USA
  • Year and Date: 2007-11-02
• [Presentation] Effect of maternal dexamethasone treatment on fetal kidney gene expression (2007)
  • Author(s): Hida M, et. al.
  • Organizer: Renal Week 2008 the American Society of Nephrology
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2007-11-02
• [Presentation] Effect of maternal nutrient restriction on fetal kidney gene expression (2007)
  • Author(s): Awazu M, et. al.
  • Organizer: Renal Week 2008 the American Society of Nephrogy
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2007-11-02
• [Presentation] Leptin induces hypertrophy of metanephric mesenchymal cells via mitogen-activated protein kinases (2007)
  • Author(s): Hida M, Awazu M et.al.
  • Organizer: 14^<th> Congress of the International Pediatric Nephrology Association
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2007-09-02
• [Presentation] Dose-dependent effects of BMP7 on proliferation, E-cadher in expression, and MAP kinase activation in a meranephric mesenchymal cell line (2007)
  • Author(s): Awazu M, Hida M.
  • Organizer: 14^<th> Congress of the International Pediatric Nephrology Association
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2007-09-02
• [Presentation] Leptin induces hypertrophy of metanephric mesenchymal cells via mitogen-activated protein kinase (2007)
  • Author(s): Hida M, et. al.
  • Organizer: 14th Congress of the International Pediatric Nephrology Associatio
  • Place of Presentation: ブタペスト
  • Year and Date: 2007-09-02
• [Presentation] レプチンのMAPキナーゼを介する後腎間葉細胞肥大作用 (2007)
  • Author(s): 飛彈麻里子,粟津緑
  • Organizer: 第50回日本腎臓学会学術総会
  • Place of Presentation: 浜松
  • Year and Date: 2007-05-26
• [Presentation] 極低出生体重児の腎機能に関する検討尿検査のみで尿細管機能評価は可能か? (2007)
  • Author(s): 森治郎、飛彈麻里子, 他
  • Organizer: 第42回日本小児腎臓病学会学術集会
  • Place of Presentation: 横浜
• [Presentation] 後腎間葉細胞の増殖、Eカドヘリン発現、MAPキナーゼ活性に対するBMP7の濃度依存性効果 (2007)
  • Author(s): 粟津緑、飛彈麻里子, 他
  • Organizer: 第42回日本小児腎臓病学会学術集会
  • Place of Presentation: 横浜
• [Presentation] 小児急性腎不全の鑑別におけるFEUNの有用性 (2007)
  • Author(s): 藤田尚代、粟津緑
  • Organizer: 第42回日本小児腎臓病学会学術集会
  • Place of Presentation: 横浜
• [Presentation] レプチンのMAPキナーゼを介する後腎間葉細胞肥大作用 (2007)
  • Author(s): 飛彈麻里子、粟津緑, 他
  • Organizer: 第42回日本小児腎臓病学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Leptin induces hypertrophy via mitogen-activated protein kinase pathways in a metanephric mesenchymal cell line (2006)
  • Author(s): Hida, M.Awazu M et.al.
  • Organizer: The American Society of Nephrology Renal Week 2006
  • Place of Presentation: Sandiego, USA
  • Year and Date: 2006-11-06
• [Presentation] Dose-dependenteffects of BMP7 on proliferation, E-cadherin expression, and MAP kinase activation in a meranephric mesenchymal cell line (2006)
  • Author(s): Awazu M, Hida M.
  • Organizer: The American Society of Nephrology Renal Week 2006
  • Place of Presentation: Sandiego, USA
  • Year and Date: 2006-11-06
• [Presentation] 胎生期シャントによるERK活性化, TGF-β発現の抑制ヒツジ胎仔尿路閉塞モデルにおける検討 (2006)
  • Author(s): 大森さゆ, 粟津緑, 北川博昭, 小池淳樹, 藤田尚代, 飛彈麻里子
  • Organizer: 第41回日本小児腎臓病学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 経口MEK阻害剤によるマウス多発性嚢胞腎進展抑制 (2006)
  • Author(s): 粟津緑, 高橋久英, 飛彈麻里子, 他
  • Organizer: 第41回日本小児腎臓病学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 尿細管上皮細胞分化・形質維持におけるJNKの役割 (2006)
  • Author(s): 藤田尚代, 大森さゆ, 飛彈麻里子, 粟津緑
  • Organizer: 第41回日本小児腎臓病学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] ヒツジ胎仔尿路閉塞モデルにおける胎生期シャントのERK活性化、TGF-b発現への影響 (2006)
  • Author(s): 大森さゆ, 藤田尚代, 飛彈麻里子, 粟津緑
  • Organizer: 第49回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] 尿細管上皮細胞分化・形質維持におけるJNKの役割 (2006)
  • Author(s): 藤田尚代、大森さゆ, 飛彈麻里子, 粟津緑
  • Organizer: 第49回日本腎臓学会学術総会
  • Place of Presentation: 東京
• [Presentation] 経口MEK阻害剤によるマウス多発性嚢胞腎進展抑制 (2006)
  • Author(s): 粟津緑、飛彈麻里子, 他
  • Organizer: 第49回日本腎臓学会学術総会
  • Place of Presentation: 東京