Molecular mechanism elucidation of iron metabolism abnormality and sarcopenia onset in chronic renal failure

• Project/Area Number: 16K16603
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: The University of Tokushima
• Principal Investigator: HORINOUCHI Yuya 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (30716593)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 慢性腎不全 / サルコペニア / 鉄 / 鉄代謝異常 / 加齢・老化

Outline of Final Research Achievements

We examined the effect of iron on Chronic Renal Failure(CRF)-related skeletal muscle atrophy. In this study, C57BL/6J mice were divided into 2 groups: Control group and Adenine-CRF group. Adenine-CRF mice showed an increase in the iron content of the skeletal muscle. The expression of transferrin receptor, an iron import receptor, and ferroportin, an iron export transporter, were downregulated in the skeletal muscle from Adenine-CRF mice. The expression of ferritin was upregulated in the skeletal muscle from Adenine-CRF mice. Adenine-CRF mice showed increased oxidative stress in the skeletal muscles. These results suggest that iron accumulation-mediated oxidative stress has the potential to accelerate skeletal muscle atrophy in CRF.

Research Products

• [Journal Article] The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease (2017)
  • Author(s): Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Journal Title: Nephrology Dialysis Transplantation Volume: - Issue: 4 Pages: 586-597
  • DOI: 10.1093/ndt/gfx252
  • Peer Reviewed / Open Access
• [Journal Article] Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest. (2017)
  • Author(s): 48)Niimura T, Zamami Y, Koyama T, Izawa-Ishizawa Y, Miyake M, Koga T, Harada K, Ohshima A, Imai T, Kondo Y, Imanishi M, Takechi K, Fukushima K, Horinouchi Y, Ikeda Y, Fujino H, Tsuchiya K, Tamaki T, Hinotsu S, Kano MR, Ishizawa K.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 17919-17919
  • DOI: 10.1038/s41598-017-17686-3
  • NAID: 120006535027
  • Peer Reviewed / Open Access
• [Journal Article] Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice (2017)
  • Author(s): Yasumasa Ikeda, Yuya Horinouchi, Hirofumi Hamano, Tasuku Hirayama, Seiji Kishi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Ken-ichi Aihara, Hideko Nagasawa, Koichiro Tsuchiya, and Toshiaki Tamaki
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 10621-10621
  • DOI: 10.1038/s41598-017-11089-0
  • NAID: 120006534998
  • Peer Reviewed / Open Access
• [Journal Article] Iron suppresses erythropoietin expression via oxidative stress-dependent hypoxia-inducible factor-2 alpha inactivation. (2017)
  • Author(s): Oshima K, Ikeda Y, Horinouchi Y, Watanabe H, Hamano H, Kihira Y, Kishi S, Izawa-Ishizawa Y, Miyamoto L, Hirayama T, Nagasawa H, Ishizawa K, Tsuchiya K, Tamaki T
  • Journal Title: Laboratory Investigation. Volume: 印刷中 Issue: 5 Pages: 555-566
  • DOI: 10.1038/labinvest.2017.11
  • NAID: 120006763916
  • Peer Reviewed
• [Journal Article] Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model. (2017)
  • Author(s): Yutaka Fukunaga, Yuki Izawa-Ishizawa, Yuya Horinouchi, Eriko Sairyo, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Yoshiro Abe, Ichiro Hashimoto, Toshiaki Tamaki.
  • Journal Title: Wound Repair and Regeneration Volume: 印刷中 Issue: 2 Pages: 217-223
  • DOI: 10.1111/wrr.12510
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 第Xa因子阻害剤の腎保護効果 (2018)
  • Author(s): 堀ノ内 裕也、池田 康将、福島 圭穣、今西 正樹、石澤 有紀、座間味 義人、藤野 裕道、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 第47回日本心脈管作動物質学会
• [Presentation] The effect of iron on skeletal muscle atrophy in chronic kidney disease (2017)
  • Author(s): Yuya Horinouchi, Yasumasa Ikeda, Hirofumi Hamano, Masaki Imanishi, Yuki Izawa-Ishizawa, Yoshito Zamami, Kenshi Takechi, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Organizer: The Society for Redox Biology and Medicine's 24th Annual Meeting
  • Int'l Joint Research
• [Presentation] 肥満・糖尿病におけるマクロファージ鉄制御機構の検討 (2017)
  • Author(s): 渡邉 大晃、池田 康将、濱野 裕章、堀ノ内 裕也、石澤 有紀、今西 正樹、座間味 義人、武智 研志、宮本 理人、土屋 浩一郎、玉置 俊晃、石澤 啓介
  • Organizer: 第132回日本薬理学会近畿部会
• [Presentation] 肥満・糖尿病におけるマクロファージ鉄の役割の検討 (2017)
  • Author(s): 渡邉 大晃、池田 康将、濱野 裕章、堀ノ内 裕也、石澤 有紀、今西 正樹、座間味 義人、武智 研志、宮本 理人、土屋 浩一郎、玉置 俊晃、石澤啓介
  • Organizer: 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
• [Presentation] 鉄摂取制限による尿細管間質障害の抑制効果の検討 (2017)
  • Author(s): 池田 康将、堀ノ内 裕也、濱野 裕章、平山 祐、岸 誠司、石澤 有紀、今西 正樹、座間味 義人、武智 研志、宮本 理人、石澤 啓介、粟飯原 賢一、永澤 秀子、土屋 浩一郎、玉置 俊晃
  • Organizer: 第41回日本鉄バイオサイエンス学会学術集会
• [Presentation] 慢性腎臓病における尿毒素蓄積によるヘプシジン制御と鉄代謝破綻のメカニズムの解明 (2017)
  • Author(s): 濱野 裕章、池田 康将、渡邉 大晃、堀ノ内 裕也、石澤 有紀、今西 正樹、座間味 義人、武智 研志、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 第41回日本鉄バイオサイエンス学会学術集会
• [Presentation] Direct activated factor X inhibitor attenuates renal fibrosis on unilateral ureteral obstruction-induced nephrotoxicity (2017)
  • Author(s): Yuya Horinouchi, Yasumasa Ikeda, Masaki Imanishi, Yoshito Zamami, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Organizer: 53rd Congress of the European Societies of Toxicology
  • Int'l Joint Research
• [Presentation] 経口FXa阻害剤の腎線維化抑制効果 (2017)
  • Author(s): 堀ノ内 裕也、池田 康将、今西 正樹、座間味 義人、石澤 有紀、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 医療薬学フォーラム 2017 第25回クリニカルファーマシーシンポジウム
• [Presentation] 第Xa因子阻害剤は腎間質線維化を抑制する (2017)
  • Author(s): 堀ノ内 裕也、池田 康将、石澤 有紀、今西 正樹、座間味 義人、武智 研志、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 第131回日本薬理学会近畿部会
• [Presentation] インドキシル硫酸蓄積はヘプシジン制御を介して鉄代謝恒常性破綻に関与する (2017)
  • Author(s): 濱野 裕章、池田 康将、渡邉 大晃、堀ノ内 裕也、石澤 有紀、今西 正樹、座間味 義人、武智 研志、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 第131回日本薬理学会近畿部会
• [Presentation] Factor Xa inhibitor attenuates renal interstitial fibrosis in mice with unilateral ureteral obstruction (2017)
  • Author(s): Yuya Horinouchi, Yasumasa Ikeda, Masaki Imanishi, Yoshito Zamami, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Organizer: The 13th Congress of the European Association for Clinical Pharmacology and Therapeutics
  • Int'l Joint Research
• [Presentation] Direct factor Xa inhibitor prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction (2017)
  • Author(s): Yasumasa Ikeda, Yuya Horinouchi, Yuki Izawa-Ishizawa, Toshiaki Tamaki
  • Organizer: 54th ERA-EDTA Congress
  • Int'l Joint Research
• [Presentation] Iron restriction prevents renal tubulointerstitial injury induced by albumin overload in mice (2017)
  • Author(s): Yasumasa Ikeda, Yuya Horinouchi, Yuki Izawa-Ishizawa, Toshiaki Tamaki
  • Organizer: 54th ERA-EDTA Congress
  • Int'l Joint Research
• [Presentation] 鉄摂取制限はタンパク過剰負荷による尿細管間質障害を抑制する (2017)
  • Author(s): 池田 康将、堀ノ内 裕也、石澤 有紀、玉置 俊晃
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] インドキシル硫酸はヘプシジンを介した鉄代謝異常に関与する (2017)
  • Author(s): 濱野 裕章、池田 康将、渡邉 大晃、堀ノ内 裕也、石澤 有紀、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] FXa阻害剤は腎間質線維化を抑制する (2017)
  • Author(s): 堀ノ内 裕也、池田 康将、石澤 有紀、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] Indoxyl sulfate involves abnormality of iron metabolism through hepcidin regulation (2017)
  • Author(s): Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Organizer: Experimental Biology 2017
  • Int'l Joint Research
• [Presentation] 新しい創薬標的としての鉄イオン (2017)
  • Author(s): 土屋 浩一郎、池田 康将、堀ノ内 裕也、石澤 有紀、宮本 理人、玉置 俊晃
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
• [Presentation] FXa阻害剤の片側尿管結紮モデルマウスにおける腎間質線維化抑制作用 (2017)
  • Author(s): 堀ノ内 裕也, 池田 康将, 石澤 有紀, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
• [Presentation] Factor Xa inhibitor attenuates renal fibrosis in mice with unilateral ureteral obstruction (2017)
  • Author(s): Horinouchi Yuya, Ikeda Yasumasa, Izawa-Ishizawa Yuki, Ishizawa Keisuke, Tsuchiya Koichiro, Tamaki Toshiaki
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール(長崎県長崎市)
• [Presentation] 慢性腎不全における尿毒素蓄積が生体内鉄代謝に与える影響の検討 (2017)
  • Author(s): 濱野 裕章, 池田 康将, 渡邉 大晃, 堀ノ内 裕也, 佐藤 明穂, 大島 啓亮, 石澤 有紀, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃
  • Organizer: 第46回日本心脈管作動物質学会年会
  • Place of Presentation: 琉球大学(沖縄県西原町)
• [Presentation] The Involvement of Iron Supplementation on Erythropoietin Expression (2016)
  • Author(s): Yasumasa Ikeda, Oshima Keisuke, Horinouchi Yuya, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
  • Organizer: Experimental Biology 2016
  • Place of Presentation: Chicago(USA)
  • Year and Date: 2016-04-02
  • Int'l Joint Research
• [Presentation] 鉄欠乏が骨格筋に与える作用の検討 (2016)
  • Author(s): 佐藤 明穂、池田 康将、濱野 裕章、堀ノ内 裕也、今尾 瑞季、渡邉 大晃、石澤 有紀、宮本 理人、石澤 啓介，玉置 俊晃、土屋 浩一郎
  • Organizer: 第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
  • Place of Presentation: 就実大学(岡山県岡山市)
• [Presentation] 骨格筋分化における鉄の役割 (2016)
  • Author(s): 池田 康将、佐藤 明穂、堀ノ内 裕也、石澤 有紀、宮本 理人、石澤 啓介、土屋 浩一郎、玉置 俊晃
  • Organizer: 第129回日本薬理学会近畿部会
  • Place of Presentation: 広島県医師会館(広島県広島市)
• [Presentation] The new insight of iron on tissue damage in metabolic disorders (2016)
  • Author(s): Yasumasa Ikeda, Yuya Horinouchi, Yuki Izawa-Ishizawa, Toshiaki Tamaki
  • Organizer: The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide/The 16th Annual Scientific Meeting of the Nitric Oxide Society of Japan
  • Place of Presentation: Sendai International Center(宮城県仙台市)
  • Int'l Joint Research
• [Remarks] 徳島大学大学院医歯薬学研究部医科学部門生理系薬理学分野
  • URL: http://www.tuyakuri.umin.jp/