Role of megalin-dependent and -independent pathways in renal protein reabsorption

• Project/Area Number: 25670409
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kyoto University
• Principal Investigator: MORI Kiyoshi 京都大学, 医学(系)研究科(研究院), 准教授 (60343232)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: メガリン / 再吸収 / アルブミン / 尿細管 / 集合管 / 糖尿病性腎症 / アルブミン尿 / ストレプトゾトシン / 腎臓学 / バイオマーカー / リポカリン

Outline of Final Research Achievements

We generated drug-inducible, proximal tubule-specific megalin knockout mice. Using these mice, we could visualize megalin-independent protein reabsorption in collecting ducts. Reabsorption of retinol-binding protein, a low molecular weight protein, was almost completed at S1-S2 segments of renal cortex. Quantitative contribution of megalin(+) S3 segment (in outer stripe of outer medulla) and megalin(-) collecting ducts for protein reabsorption was relatively very small. Further analysis is required to investigate whether protein reabsorption at collecting ducts elicits inflammatory signals in those cells.

Research Products

• [Journal Article] An AKI biomarker lipocalin 2 in the blood derives from the kidney in renal injury but from neutrophils in normal and infected conditions. (2014)
  • Author(s): Kanda J, Mori K, Kawabata H et al.
  • Journal Title: Clin Exp Nephrol Volume: 未定
  • NAID: 120005678175
  • Peer Reviewed
• [Journal Article] Neutrophil gelatinase-associated lipocalin in idiopathic pulmonary fibrosis. (2014)
  • Author(s): Ikezoe K, Handa T, Mori K et al.
  • Journal Title: Eur Respir J Volume: 未定
  • Peer Reviewed
• [Journal Article] Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases. (2014)
  • Author(s): Kuwabara T, Mori K et al.
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] Secreted protein lipocalin-2 promotes microglial M1 polarization. (2013)
  • Author(s): Jang E, Lee S, Mori K et al.
  • Journal Title: Faseb J Volume: 27 Pages: 1176-1190
  • Peer Reviewed
• [Presentation] 糖尿病性腎症の微量アルブミン尿期に糸球体濾過されるアルブミンの増加は微量ではない (2015)
  • Author(s): 森慶太, 森潔, 笠原正登, 横井秀基, 桑原孝成, 今牧博貴, 石井輝, 戸田尚宏, 中尾一和, 柳田素子, 向山政志
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21 – 2015-05-24
• [Presentation] 糖尿病症例で尿中微量アルブミンを測らない４つの理由 (2015)
  • Author(s): 森 潔
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21 – 2015-05-24
  • Invited
• [Presentation] 糸球体および近位尿細管に全く障害がないモデルにおける蛋白再吸収阻害の影響 (2014)
  • Author(s): 森慶太, 森潔, 笠原正登, 横井秀基, 桑原孝成, 今牧博貴, 石井輝, 戸田尚宏, 中尾一和, 柳田素子, 向山政志
  • Organizer: 日本腎臓学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 糖尿病性腎症進展に果たす自然炎症の役割とその活性化機序~脂質,RA系そして細胞間クロストーク~ (2014)
  • Author(s): 桑原孝成, 森潔, 笠原正登, 中尾一和, 柳田素子, 向山政志
  • Organizer: 日本腎臓学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 糸球体および近位尿細管に全く障害がないモデルにおける蛋白再吸収阻害の影響 (2014)
  • Author(s): 森慶太、森 潔、笠原正登ほか
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 薬剤誘導性ノックアウトマウスを用いた蛋白尿における腎近位尿細管と下流ネフロンの蛋白再吸収能評価 (2014)
  • Author(s): 森慶太、森 潔、笠原正登ほか
  • Organizer: 日本臨床分子医学会学術集会
  • Place of Presentation: 東京
• [Presentation] megalin依存性および非依存性経路による腎臓における低分子量蛋白の再吸収 (2013)
  • Author(s): 森慶太、森 潔、向山政志ほか
  • Organizer: 日本腎臓学会学術総会
  • Place of Presentation: 東京