The mechanism of mitochondrial injury and iron overload induced hepatocarcinogenesis in the post hepatic virus.

• Project/Area Number: 25461019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: korenaga Masaaki 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (70420536)
• Co-Investigator(Kenkyū-buntansha): MURATA KAZUMOTO 国立研究開発法人国立国際医療研究センター, その他部局等, その他 (40345971)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 酸化ストレス / ミトコンドリア障害 / 脂肪肝 / 鉄過剰 / 脾臓

Outline of Final Research Achievements

The inhibition of COX7a2 in mitochondrial complex IV might induce hepatic oxidative stress, fat accumulation, and iron metabolic disorder.Deferasirox improved hepatic ballooning reduced liver fibrosis in STAM miceHowever, long term treatment of Deferasirox could not inhibit the development of liver tumors.

Research Products

• [Journal Article] The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus (2016)
  • Author(s): Ueyama, M., Nishida, N., Korenaga, M., Korenaga, K., Kumagai, E., et al.
  • Journal Title: Journal of Gastroenterology Volume: 51 Issue: 4 Pages: 370-379
  • DOI: 10.1007/s00535-015-1116-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice. (2015)
  • Author(s): Korenaga M, Nishina S, Korenaga K, Tomiyama Y, Yoshioka N, Hara Y, Sasaki Y, Shimonaka Y, Hino K.
  • Journal Title: Liver Int. Volume: 35 Issue: 4 Pages: 1303-14
  • DOI: 10.1111/liv.12675
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice. (2015)
  • Author(s): Korenaga M, Nishina S, Korenaga K, Tomiyama Y, Yoshioka N, Hara Y, Sasaki Y, Shimonaka Y, Hino K
  • Journal Title: Liver Int Volume: 35 Pages: 1303-14
  • Peer Reviewed / Open Access
• [Journal Article] High-throughput and sensitive next-generation droplet digital PCR assay for the quantitation of the hepatitis C virus mutation at core amino acid 70. (2014)
  • Author(s): Mukaide M, Sugiyama M, Korenaga M, Murata K, Kanto T, Masaki N, Mizokami M
  • Journal Title: J Virol Methods Volume: 207 Pages: 169-77
  • Peer Reviewed / Open Access
• [Journal Article] Clinical usefulness of non-protein respiratory quotient measurement in non-alcoholic fatty liver disease (2013)
  • Author(s): Korenaga K1, Korenaga M, Teramoto F, Suzuki T, Nishina S, Sasaki K, Nakashima Y, Tomiyama Y, Yoshioka N, Hara Y, Moriya T, Hino K.
  • Journal Title: Hepatol Res. Volume: 43 Issue: 12 Pages: 1284-1294
  • DOI: 10.1111/hepr.12095
  • Peer Reviewed
• [Presentation] 分岐鎖アミノ酸の酸化ストレス抑制作用と発癌抑止 (2014)
  • Author(s): 是永匡紹
  • Organizer: 第40回日本肝臓学会東部会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-27
  • Invited
• [Presentation] 糖尿病関連遺伝子多型と肝硬度測定を用いた非B非C肝病態促進症例の囲い込み (2014)
  • Author(s): 是永匡紹 西田奈央 溝上雅史
  • Organizer: Japan Digestive Disease Week (JDDW) 2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-25
• [Presentation] 肝内脂肪蓄積に関与する脾臓内鉄濃度と肝ミトコンドリア呼吸鎖複合体IV障害 (2014)
  • Author(s): 是永匡紹、杉山真也、辻美保子、近藤美幸、由雄祥代、是永圭子、村田一素、考藤達哉、正木尚彦、溝上雅史
  • Organizer: 第50回日本肝蔵学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] 糖尿病関連SNPsとPNPLA3を用いた糖尿病合併肝病態促進症例の囲い込み (2014)
  • Author(s): 是永匡紹 西田奈央 是永圭子 竹田 努 青木孝彦 由雄祥代 山極洋子 杉山真也 今村雅俊 柳内秀勝 山田慎吾 川口巧 佐田通夫 村田一素 考藤達哉 正木尚彦 溝上雅史
  • Organizer: 第50回日本肝蔵学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] 慢性肝疾患におけるamino acid imbalanceとインスリン抵抗性・酸化ストレスのクロストーク (2013)
  • Author(s): 是永匡紹 是永圭子 竹田努 山極洋子 今村雅俊 村田一素 正木尚彦 溝上雅史
  • Organizer: 第49回日本肝蔵学会総会
  • Place of Presentation: 東京
• [Presentation] C 型慢性肝疾患における分岐鎖アミノ酸の酸化ストレス抑制作用 (2013)
  • Author(s): 是永 匡紹
  • Organizer: 第49回日本肝蔵学会総会
  • Place of Presentation: 東京
  • Invited
• [Funded Workshop] The Liver Meeting® 2015 (2015)
  • Place of Presentation: San Francisco、USA
  • Year and Date: 2015-11-13