The roles of autophagy in liver regenetion in a steatotic liver

• Project/Area Number: 15K10167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: IKEGAMI Toru 九州大学, 大学病院, 講師 (80432938)
• Co-Investigator(Kenkyū-buntansha): 副島 雄二 九州大学, 大学病院, 助教 (30325526) ; 池田 哲夫 九州大学, 大学病院, 准教授 (60585701) ; 調 憲 群馬大学, 大学院医学系研究科, 教授 (70264025) ; 吉住 朋晴 九州大学, 医学研究院, 准教授 (80363373)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝再生 / オートファジー / 脂肪肝 / 肝切除

Outline of Final Research Achievements

Murine autophagy suppressed model with Atg5 gene knock out was created using Cre-lox system, followed by hepatic resection and serial sampling of the regenerating liver tissues. It revealed reducedheaptic BrdU intake, accumulated p62 protein (injured protein), lowered serum albumin, p21 protein associated delayed cell cycle turn over with rescued G2 and S, and lower repression of Cyclone D1. These observation was also confirmed using fatty liver autophagy Ko model. In abnormal liver condition including massive heaptectomy, fatty liver, non-alchholic steatosis, diabetes associated liver disease, autophagy is significantly suppressed and smooth regeneration was impaired.

Research Products

• [Journal Article] p62 Promotes Amino Acid Sensitivity of mTOR Pathway and Hepatic Differentiation in Adult Liver Stem/Progenitor Cells. (2017)
  • Author(s): Sugiyama M, Yoshizumi T, Yoshida Y, Bekki Y, Matsumoto Y, Yoshiya S, Toshima T, Ikegami T, Itoh S, Harimoto N, Okano S, Soejima Y, Shirabe K, Maehara Y.
  • Journal Title: J Cell Physiol. Volume: 232 Issue: 8 Pages: 2112-2124
  • DOI: 10.1002/jcp.25653
  • Peer Reviewed
• [Journal Article] Surgical Resection for Lymph Node Metastasis After Liver Transplantation for Hepatocellular Carcinoma. (2017)
  • Author(s): Ikegami T, Yoshizumi T, Kawasaki J, Nagatsu A, Uchiyama H, Harada N, Harimoto N, Itoh S, Motomura T, Soejima Y, Maehara Y.
  • Journal Title: Anticancer Res. Volume: 37 Pages: 891-895
  • Peer Reviewed
• [Journal Article] Treatment with sofosbuvir and ledipasvir without ribavirin for 12?weeks is highly effective for recurrent hepatitis C virus genotype 1b infection after living donor liver transplantation: a Japanese multicenter experience (2017)
  • Author(s): Ueda Yoshihide、Ikegami Toru、Akamatsu Nobuhisa、Soyama Akihiko、Shinoda Masahiro、Goto Ryoichi、Okajima Hideaki、Yoshizumi Tomoharu、Taketomi Akinobu、Kitagawa Yuko、Eguchi Susumu、Kokudo Norihiro、Uemoto Shinji、Maehara Yoshihiko
  • Journal Title: Journal of Gastroenterology Volume: 52 Issue: 8 Pages: 986-991
  • DOI: 10.1007/s00535-017-1310-9
  • Peer Reviewed
• [Journal Article] Hepatic stellate cells secrete WFA+ -M2BP; its role in biological interactions with Kupffer cells. (2017)
  • Author(s): Bekki Y,, Yoshizumi T, Shimoda S, Itoh S, Harimoto N, Ikegami T, Kuno A, Narimatsu H, Shirabe K, Maehara Y.
  • Journal Title: J Gastroenterol Hepatol Volume: 32 Issue: 7 Pages: 1387-1393
  • DOI: 10.1111/jgh.13708
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Eversion Technique to Prevent Biliary Stricture After Living Donor Liver Transplantation in the Universal Minimal Hilar Dissection Era. (2017)
  • Author(s): kegami T, Shimagaki T, Kawasaki J, Yoshizumi T, Uchiyama H, Harada N, Harimoto N, Itoh S, Soejima Y, Maehara Y.
  • Journal Title: Transplantation Volume: 101 Issue: 1 Pages: e20-e25
  • DOI: 10.1097/tp.0000000000001533
  • Peer Reviewed
• [Journal Article] Telaprevir versus simeprevir for the treatment of recurrent hepatitis C after living donor liver transplantation. (2016)
  • Author(s): Ikegami T, Yoshizumi T, Yoshida Y, Kurihara T, Harimoto N, Itoh S, Shimokawa M, Fukuhara T, Shirabe K, Maehara Y
  • Journal Title: Hepatol Res. Volume: 46(3) Issue: 3
  • DOI: 10.1111/hepr.12546
  • Peer Reviewed
• [Journal Article] Telaprevir versus simeprevir for the treatment of recurrent hepatitis C after living donor liver transplantation. (2016)
  • Author(s): Ikegami T, Yoshizumi T, Yoshida Y, Kurihara T, Harimoto N, Itoh S, Shimokawa M, Fukuhara T, Shirabe K, Maehara Y.
  • Journal Title: Hepatol Res Volume: 46
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Natural killer cells regulate T cell immune responses in primary biliary cirrhosis. (2015)
  • Author(s): Shimoda S, Hisamoto S, Harada K, Iwasaka S, Chong Y, Nakamura M, Bekki Y, Yoshizumi T, Shirabe K, Ikegami T, Maehara Y, He XS, Gershwin ME, Akashi K.
  • Journal Title: Hepatology. Volume: 62 Issue: 6 Pages: 1817-1827
  • DOI: 10.1002/hep.28122
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Suppression of silent information regulator 1 activity in noncancerous tissues of hepatocellular carcinoma: Possible association with non-B non-C hepatitis pathogenesis. (2015)
  • Author(s): Konishi H, Shirabe K, Nakagawara H, Harimoto N, Yamashita YI, Ikegami T, Yoshizumi T, Soejima Y, Oda Y, Maehara Y.
  • Journal Title: Cancer Science Volume: 印刷中 Issue: 5 Pages: 542-549
  • DOI: 10.1111/cas.12653
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP), for assessing liver fibrosis. (2015)
  • Author(s): Toshima T, Shirabe K, Ikegami T, et al.
  • Journal Title: Journal of Gastroenterology Volume: 50 Issue: 1 Pages: 76-84
  • DOI: 10.1007/s00535-014-0946-y
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy. (2014)
  • Author(s): Umemoto Y, Okano S, Matsumoto Y, Nakagawara H, Matono R, Yoshiya S, Yamashita YI, Yoshizumi T, Ikegami T, Soejima Y, Harada M, Aishima S, Oda Y, Shirabe K, Maehara Y.
  • Journal Title: J Gastroenterol. Volume: not determined Issue: 1 Pages: 65-75
  • DOI: 10.1007/s00535-014-0933-3
  • Peer Reviewed / Open Access
• [Presentation] How to reduce biliary stricture in LDLT; Kyushu style. (2017)
  • Author(s): Ikegami T, Yoshizumi T, Harimoto N, Harada N, Itoh S, Toshima T, Motomura T, Mano Y, Soejima Y, Maehara Y
  • Organizer: Asian Transplantation Week 2017
  • Int'l Joint Research / Invited
• [Presentation] Left lobe living donor liver transplantation - Kyushu University Technique. International meeting on living donor liver transplantation (2017)
  • Author(s): Ikegami T, Yoshizumi T, Harimoto N, Harada N, Itoh S, Toshima T, Motomura T, Mano Y, Soejima Y, Maehara Y
  • Organizer: International living donor liver transplantation study group 2017
  • Int'l Joint Research / Invited
• [Presentation] timal volumetric assessment of liver volume. (2017)
  • Author(s): Ikegami T, Yoshizumi T, Harimoto N, Harada N, Itoh S, Toshima T, Motomura T, Mano Y, Soejima Y, Maehara Y
  • Organizer: International living donor liver transplantation study group 2017
  • Int'l Joint Research / Invited
• [Presentation] 生体肝移植後C型肝炎再発に対するDAAを用いた治療. (2017)
  • Author(s): 78.池上 徹, 吉住朋晴, 前原喜彦
  • Organizer: 第25回日本消化器関連学会週間
• [Presentation] 肝移植後C型肝炎の再発予防策 (2017)
  • Author(s): 池上 徹, 吉住朋晴, 本村貴志, 間野洋平, 長津明久, 伊藤心二, 原田 昇, 播本憲史, 後町武志, 副島雄二, 前原喜彦
  • Organizer: 第53回日本移植学会総会
• [Presentation] NADPH oxidaseおよびToll like receptor4制御による脂肪肝温阻血再灌流傷害の改善 (2015)
  • Author(s): 木村 光一, 栗原 健, 吉田 佳弘, 今井 大祐, 別城 悠樹, 松本 佳大, 武石 一樹, 伊藤 心二, 播本 憲史, 山下 洋市, 池上 徹, 吉住 朋晴, 川中 博文, 調 憲, 前原 喜彦
  • Organizer: 日本移植学会
  • Place of Presentation: 熊本
  • Year and Date: 2015-10-01
• [Presentation] Left lobe living donor liver transplantation - Kyushu University (2015)
  • Author(s): Toru Ikegami, Hideaki Uchiyama, Tomoharu Yoshizumi, Yuji Soejima, Ken Shirabe, Yoshihiko Maehara
  • Organizer: International meeting on living donor liver transplantation
  • Place of Presentation: Barcelona
  • Year and Date: 2015-09-28
  • Int'l Joint Research / Invited
• [Presentation] Various types of living donor liver resection in Japan (2015)
  • Author(s): Toru Ikegami, Ken Shirabe, Tomoharu Yoshizumi, Yuji Soejima Hideaki Uchiyama, Yo-ichi Yamashita, Yoshihiko Maehara
  • Organizer: The liver week 2015
  • Place of Presentation: Busan
  • Year and Date: 2015-09-10
  • Int'l Joint Research / Invited
• [Presentation] 上皮性成長因子(EGF)遺伝子の一塩基多型がHCV患者の肝細胞癌の肝切除後再発に及ぼす影響 (2015)
  • Author(s): 別城 悠樹, 今井 大祐, 王 歓林, 木村 光一, 松本 佳大, 中川原 英和, 吉屋 匠平, 井口 友宏, 二宮 瑞樹, 山下 洋市, 池上 徹, 吉住 朋晴, 岡野 慎士, 川中 博文, 調 憲, 前原 喜彦
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-16
• [Presentation] 肝移植におけるイノベーション 生体肝移植後成績向上を目指した治療戦略の構築 (2015)
  • Author(s): 吉住 朋晴, 調 憲, 池上 徹, 二宮 瑞樹, 山下 洋市, 井口 友宏, 副島 雄二, 内山 秀昭, 今井 大祐, 別城 悠樹, 王 歓林, 木村 光一, 中川原 英和, 松本 佳大, 吉屋 匠平, 播本 憲史, 池田 哲夫, 岡野 慎士, 川中 博文, 前原 喜彦
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-16
• [Remarks] 九州大学 消化器総合外科 研究部門
  • URL: http://www.kyudai2geka.com/html/kenkyu/kenkyu.html