The therapeutic starategy by Ghrelin targeting against mitochondria dynamics

• Project/Area Number: 26670433
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Wakino Shu 慶應義塾大学, 医学部, 准教授 (50265823)
• Co-Investigator(Kenkyū-buntansha): Shinozuka Keisuke 慶應義塾大学, 医学部, 助教 (00594558) ; Itoh Hiroshi 慶應義塾大学, 医学部, 教授 (40252457)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: グレリン / ミトコンドリア / マイトファジ― / fission / fusion / マイトファジー / 内科 / 糖尿病

Outline of Final Research Achievements

Ghrelin have protective effects against renal impairment by reducing renal mitochondria-derived oxidative stress and by improving mitochondrial function. Recent study revealed that mitochondria dynamics plays an important role in the initiation and progression of renal failure. We investigate the efficacy of Ghrelin for the treatment of diabetic kidney impairment. C57BL/6 mice at the age of 8 weeks were subjected to streptozotosin injection in order to render diabetic. After the onset of diabetes, Ghrelin at the dose of 300μg/kg was administered by daily intraperitoneal injection. We found that swelling of mitochondria and the disruption of mitochondrial cristae in the kidney were ameliorated by the treatment with Ghrelin. Ghrelin increased the expressions of genes related to mitophagy including PINK1 and Perkin, although it did not have any effect on the genes related to mitochondria fission or fusion. We concluded that Ghrelin has renal protective effects in diabetic kidney disease.

Research Products

• [Presentation] 心血管系ペプチドのトランスレーショナルリサーチ グレリンの腎保護作用と慢性腎臓病患者への応用 (2015)
  • Author(s): 脇野 修, 中谷 英章, 藤村 慶子, 篠塚 圭祐, 伊藤 裕
  • Organizer: 第19回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-10
  • Invited
• [Presentation] グレリンによるミトコンドリアエピゲノム制御を介したCKDモデルマウスの身体能力改善 (2015)
  • Author(s): 田蒔 昌憲, 宮下 和季, 脇野 修, 三石 正憲, 林 晃一, 伊藤 裕
  • Organizer: 第５８回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] 消化管ペプチドGhrelinの酸化ストレス抑制を介した腎保護作用 (2015)
  • Author(s): 藤村 慶子, 脇野 修, 長谷川 一宏, 水口 斉, 篠塚 圭祐, 林 晃一, 伊藤 裕
  • Organizer: 第５８回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] グレリン受容体の血中脂質への影響 (2015)
  • Author(s): 浦井 秀徳, 神田 武志, 徳山 博文, 脇野 修, 伊藤 裕
  • Organizer: 第52回日本臨床分子医学会学術総会
  • Place of Presentation: みやこメッセ（京都府京都市）
  • Year and Date: 2015-04-10
• [Presentation] 慢性腎臓病の腎筋連関による身体能力低下と消化管ホルモングレリンの治療効果 (2015)
  • Author(s): 田蒔 昌憲, 宮下 和季, 脇野 修, 三石 正憲, 林 晃一, 伊藤 裕
  • Organizer: 第52回日本臨床分子医学会学術総会
  • Place of Presentation: みやこメッセ（京都府京都市）
  • Year and Date: 2015-04-10