Regulation of aged liver regenerative disorder focused of epigenetic changes

• Project/Area Number: 25462091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokushima
• Principal Investigator: MORINE Yuji 徳島大学, 大学院医歯薬学研究部, 講師 (60398021)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Mitsuo 徳島大学, 大学院医歯薬学研究部, 教授 (10216070) ; IMURA Satoru 徳島大学, 病院, 特任教授 (90380021) ; IKEMOTO Tetsuya 徳島大学, 大学院医歯薬学研究部, 助教 (20398019) ; UTSUNOMIYA Toru 徳島大学, 大学院医歯薬学研究部, 准教授 (30304801)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Epigenetics / HDAC / 肝再生 / 加齢 / 肝切除

Outline of Final Research Achievements

Mechanism of the decreased regenerative capacity of aged liver after hepatectemy and its regulation focused on epigenetic changes were elucidated in this study. In aged liver, the down-regulated of cell cycle and up -regulated of apoptosis-related genes during liver regeneration after hepatectomy were demonstrated. Also the epigenetic regulation with HDAC inhibitor up-regulated cell cycle related genes and differentiation related genes, after hepatectomy resulted in increase of liver regeneration and decrease of liver injury.

Research Products

• [Journal Article] Liver regeneration after splenectomy in patients with liver cirrhosis. (2016)
  • Author(s): Yamada S, Morine Y, Imura S, Ikemoto T, Arakawa Y, Iwahashi S, Saito Y, Yoshikawa M, Teraoku H, Shimada M.
  • Journal Title: Hepatol Res. Volume: 印刷中 Pages: 443-449
  • DOI: 10.1111/hepr.12573
  • Peer Reviewed
• [Journal Article] The value of systematic lymph node dissection for intrahepatic cholangiocarcinoma from the viewpoint of liver lymphatics. (2015)
  • Author(s): Y.Morine, M.Shimada
  • Journal Title: Journal of Gastroenterology Volume: 50 Pages: 913-927
  • DOI: 10.1007/s00535-015-1071-2
  • Peer Reviewed
• [Journal Article] Clinical role of Foxp3⁺regulatory T cell in Living donor related liver transplantation for prediction of life-threatening complications (2015)
  • Author(s): Asanoma M, Mori H, Ikemoto T, Utsunomiya T, Imura S, Morine Y, Hanaoka J, Kanamoto M, Saito Y, Yamada S, Shimada M.
  • Journal Title: J. Med. Invest. Volume: 62 Issue: 1.2 Pages: 37-40
  • DOI: 10.2152/jmi.62.37
  • NAID: 130005129689
  • Peer Reviewed
• [Journal Article] Dysfunction of liver regeneration in aged liver after partial hepatectomy (2015)
  • Author(s): Enkhbold C1, Morine Y, Utsunomiya T, Imura S, Ikemoto T, Arakawa Y, Saito Y, Yamada S, Ishikawa D, Shimada M.
  • Journal Title: Journal of gastroenterology and hepatology Volume: - Pages: 1217-1224
  • DOI: 10.1111/jgh.12930
  • Peer Reviewed
• [Journal Article] Recovery of nutritional metabolism after liver transplantation (2015)
  • Author(s): Sugihara K, Yamanaka-Okumura H, Teramoto A, Urano E, Katayama T, Morine Y, Imura S, Utsunomiya T, Shimada M, Takeda E.
  • Journal Title: Nutrition Volume: 31 Pages: 105-110
  • DOI: 10.1016/j.nut.2014.05.016
  • Peer Reviewed
• [Journal Article] Evaluation and management of hepatic injury induced by oxaliplatin-based chemotherapy in patients with hepatic resection for colorectal liver metastasis. (2014)
  • Author(s): Morine Y, Shimada M, Utsunomiya T.
  • Journal Title: Hepatology Research Volume: 44 Pages: 59-69
  • DOI: 10.1111/hepr.12107
  • Peer Reviewed
• [Journal Article] Senescence-related genes may be responsible for poor liver regeneration after hepatectomy in elderly patients. (2014)
  • Author(s): Zhu C, Ikemoto T, Utsunomiya T, Yamada S, Morine Y, Imura S, Arakawa Y, Takasu C, Ishikawa D, Shimada M
  • Journal Title: J Gastroenterol Hepatol. Volume: 29(5) Pages: 1102-1108
  • DOI: 10.1111/jgh.12468
  • Peer Reviewed
• [Journal Article] G Beneficial effects of enteral nutrition containing with hydrolyzed whey peptide on warm ischemia/reperfusion injury in the rat liver. (2014)
  • Author(s): Hanaoka J, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H, Sugimoto K, Saito Y, Yamada S
  • Journal Title: Hepatol Res. Volume: 44(1) Pages: 114-121
  • DOI: 10.1111/hepr.12097
  • Peer Reviewed
• [Journal Article] Beneficial effects of green tea catechin on massive hepatectomy model in rats. (2014)
  • Author(s): Saito Y, Mori H, Takasu C, Komatsu M, Hanaoka J, Yamada S, Asanoma M, Ikemoto T, Imura S, Morine Y, Utsunomiya T, Shimada M.
  • Journal Title: Journal of Gastroenterology Volume: -
  • Peer Reviewed
• [Journal Article] Clinical features of pancreaticobiliary maljunction: update analysis of 2nd Japan-nationwide survey. (2013)
  • Author(s): Morine Y, Shimada M, Takamatsu H, Araida T, Endo I, Kubota M, Toki A, Noda T, Matsumura T, Miyakawa S, Ishibashi H, Kamisawa T, Shimada H.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 20 Pages: 472-480
  • DOI: 10.1007/s00534-013-0606-2
  • NAID: 10031183502
  • Peer Reviewed
• [Journal Article] Significance of sonic hedgehog signaling after massive hepatectomy in a rat (2013)
  • Author(s): Jun Hanaoka
  • Journal Title: Surg Today Volume: 50 Pages: 300-307
  • DOI: 10.1007/s00595-012-0248-z
  • NAID: 10031168007
  • Peer Reviewed
• [Presentation] 小胞体ストレス応答に着目した加齢肝再生不全における肝星細胞の役割についての検討 (2015)
  • Author(s): 荒川悠佑,島田光生,吉川雅登,寺奥大貴,山田眞一郎,,齋藤裕,岩橋衆一,池本哲也,森根裕二,居村暁
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2015-07-16
• [Presentation] 肝胆膵外科手術における周術期栄養評価の有用性に関する研究－体成分分析装置と主観的包括的アセスメントSGA－ (2015)
  • Author(s): 齋藤 裕
  • Organizer: 第52回日本外科代謝栄養学会学術集会
  • Place of Presentation: きゅりあん（東京都品川区）
  • Year and Date: 2015-07-02
• [Presentation] 肝胆膵外科手術におけるNST介入による周術期栄養評価 (2015)
  • Author(s): 齋藤裕,安井苑子,吉川雅登,寺奥大貴,山田眞一郎,岩橋衆一,荒川悠佑,池本哲也,森根裕二,居村暁,濱田康弘,島田光生
  • Organizer: 第40回日本外科系連合学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-06-19
• [Presentation] 肝胆膵外科手術における周術期栄養評価の有用性に関する研究‐体成分分析装置と主観的包括的アセスメント- (2015)
  • Author(s): 齋藤裕,安井苑子,吉川雅登,寺奥大貴,山田眞一郎,岩橋衆一,荒川悠佑,池本哲也,森根裕二,居村暁,濱田康弘,島田光生
  • Organizer: 第27回日本肝胆膵外科学会
  • Place of Presentation: ホテルグランパシフィックLE DAIBA（東京都港区）
  • Year and Date: 2015-06-13
• [Presentation] 脾機能亢進症を合併した肝癌に対する脾摘＋肝切除の有用性 (2015)
  • Author(s): 山田眞一郎,吉川雅登,寺奥大貴,齋藤裕,高須千絵,岩橋衆一,荒川悠佑,東島潤,池本哲也,居村暁,森根裕二,島田光生
  • Organizer: 第27回日本肝胆膵外科学会
  • Place of Presentation: ホテルグランパシフィックLE DAIBA（東京都港区）
  • Year and Date: 2015-06-13
• [Presentation] 加齢肝再生不全における肝星細胞の役割についての検討 (2015)
  • Author(s): 荒川悠佑,島田光生,寺奥大貴,吉川雅登,石川大地,山田眞一郎,齋藤裕,高須千絵,岩橋衆一,池本哲也,森根裕二,居村暁,東島潤
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-16
• [Presentation] 肝虚血再灌流傷害の発生・進展機序の解明と統合的治療法開発の取り組み (2015)
  • Author(s): 髙須千絵,森根裕二,居村暁,荒川悠佑,岩橋衆一,齋藤裕,山田眞一郎,石川大地,島田光生
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-16
• [Presentation] 高齢者の肝再生不全の機序解明と治療への応用 (2013)
  • Author(s): 荒川悠佑, 島田光生, 石川大地, 山田眞一郎, 淺野間理仁, 齋藤裕, 岩橋衆一, 金本真美, 森大樹, 池本哲也, 森根裕二, 居村暁,
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場(福岡県)
• [Presentation] 脂肪由来幹細胞を用いた肝胆膵領域の再生医療に関するimpactと課題 (2013)
  • Author(s): 池本哲也 島田光生, 宇都宮徹, 居村暁, 森根裕二, 森大樹, 荒川悠佑, 金本真美, 齋藤裕, 山田眞一郎, 淺野間理仁, 三宅秀則
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場(福岡県)
• [Presentation] 高齢者の肝再生不全の機序解明と治療への応用 (2013)
  • Author(s): 荒川悠佑, 島田光生, 石川大地, 山田眞一郎, 髙須千絵, 齋藤裕, 岩橋衆一, 金本真美, 池本哲也, 森根裕二, 居村暁, 宇都宮徹,
  • Organizer: 第43回日本創傷治癒学会
  • Place of Presentation: 別府湾ロイヤルホテル(大分県)