Epigenetic analysis for reno-musclar correlation and optimal hormonal treatment for physical decline in patients with chronic kidney disease

• Project/Area Number: 26860644
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: TAMAKI MASANORI 慶應義塾大学, 医学部, 助教 (90528902)
• Research Collaborator: MIYASHITA Kazutoshi ; WAKINO Shu ; ITOH Hiroshi
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 慢性腎臓病 / グレリン / PGC-1α / ミトコンドリア / エピゲノム / マイトペニア / TNF-α / 慢性腎臓病(CKD) / 身体能力

Outline of Final Research Achievements

A physical decline not only led to lowering quality of life, but also raised risk of all-cause mortality. Chronic kidney disease (CKD) impaired physical performance associated with muscle alteration (reno-muscular correlation) since the early stage. 5/6 nephrectomized mice (5/6Nx mice), a mild CKD model, was shown that decrease in exercise endurance associated with decrease in muscular mitochondria (mitopenia) preceded decrease in muscle strength associated with muscle atrophy. TNF-α, a representative inflammatory cytokine which was increased since the early stage of CKD, was supposed as a candidate of mitopenia. Acylated ghrelin treatment, a gastric hormone, not only increased muscle strength and muscle mass, but improved exercise endurance and mitopenia through epigenetic modification of PGC-1α gene in 5/6Nx mice. Meanwhile, IGF-1 treatment, a muscle anabolic factor, hardly improved exercise endurance and did not improve mitopenia, though increased muscle strength and muscle mass.

Research Products

• [Journal Article] Improvement of physical performance in 5/6 nephrectomized CKD model mice by a gastric hormone ghrelin. (2015)
  • Author(s): Tamaki M, Miyashita K, Wakino S, Hagiwara A, Inoue H, Fujii K, Fujii C, Mitsuishi M, Muraki A, Hayashi K, Doi T, Itoh H.
  • Journal Title: Endocrinology Volume: 156 Issue: 10 Pages: 3638-3648
  • DOI: 10.1210/en.2015-1353
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CKDに伴う代謝変調と腎筋連関 (2015)
  • Author(s): 宮下和季、田蒔昌憲、脇野 修、伊藤 裕
  • Journal Title: Annual Review 腎臓 2015 Volume: 2015 Pages: 164-172
• [Presentation] グレリンによる慢性腎臓病マウスの身体能力改善におけるミトコンドリアエピゲノム制御の意義 (2016)
  • Author(s): 田蒔 昌憲，萩原 あいか，宮下 和季，脇野 修，土井 俊夫，伊藤 裕
  • Organizer: 第89回日本内分泌学会学術集会
  • Place of Presentation: 国立京都国際会館(京都府京都市)
  • Year and Date: 2016-04-21
• [Presentation] Improvement of physical decline through combined effects of muscle enhancement and mitochondrial activation by a gastric hormone ghrelin in male 5/6Nx CKD model mice (2015)
  • Author(s): 田蒔 昌憲，萩原 あいか，宮下 和季，脇野 修，井上 博之，藤井 健太郎，藤井 千華子，佐藤 正明，三石正憲，村木 絢子，林 晃一，土井 俊夫，伊藤 裕
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館(愛媛県松山市)
  • Year and Date: 2015-10-09
• [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] Improvement of physical performance in 5/6 nephrectomized CKD model mice through epigenetic modulation of PGC-1a expression by ghrelin treatment (2015)
  • Author(s): Masanori Tamaki, Kazutoshi Miyashita, Shu Wakino, Masanori Mitsuishi, Koichi Hayashi, Hiroshi Itoh
  • Organizer: 52th ERA-EDTA (European Renal Association – European Dialysis Therapy Association) Congress.
  • Place of Presentation: ロンドン(イギリス)
  • Year and Date: 2015-05-28
  • Int'l Joint Research
• [Presentation] グレリンはミトコンドリアエピゲノム制御を介して慢性腎臓病マウスの身体能力を改善する (2014)
  • 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18回日本心血管内分泌代謝学会総会
  • Place of Presentation: 横浜市開港記念会館(神奈川県横浜市)
  • Year and Date: 2014-11-21 – 2014-11-22
• [Presentation] Exercise endurance of 5/6 nephrectomized mice was improved by gastric hormone ghrelin through PGC1α-dependent activation of muscle mitochondria. (2014)
  • Author(s): Masanori Tamaki, Kazutoshi Miyashita, Shu Wakino, Masanori Mitsuishi, Koichi Hayashi and Hiroshi Itoh
  • Organizer: 16th International Congress of Endocrynology, The Endocrine Society’s 96th Annual Meeting & Expo
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2014-06-21 – 2014-06-24
• [Book] 最新透析医療：先端技術との融合. (2016)
  • Author(s): 田蒔 昌憲，宮下 和季，伊藤 裕
  • Total Pages: 860
  • Publisher: 医薬ジャーナル社