Impact of autophagy in liver regeneration

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591989
• 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: YOSHIZUMI Tomoharu 九州大学, 大学病院, 講師 (80363373)
• Co-Investigator(Kenkyū-buntansha): SHIRABE Ken 九州大学, 医学研究院, 准教授 (70264025) ; IKEGAMI Toru 九州大学, 医学研究院, 助教 (80432938) ; YAMASHITA Yo-ichi 九州大学, 医学研究院, 助教 (00404070) ; HARIMOTO Norifumi 九州大学, 医学研究院, 助教 (00419582) ; UCHIYAMA Hideaki 九州大学, 医学研究院, その他 (70380425) ; SOEJIMA Yuji 九州大学, 医学研究院, 共同研究員 (30325526) ; NINOMIYA Mizuki 九州大学, 医学研究院, 助教 (30546461) ; TAKETOMI Akinobu 九州大学, 医学研究院, 講師 (70363364) ; MAEHARA Yoshihiko 九州大学, 医学研究院, 教授 (80165662)
• Project Period (FY): 2011 – 2013
• Keywords: 肝臓外科学

Research Abstract

We investigated the activity of autophagy-associated pathways in liver regeneration after partial hepatectomy (PHx) in liver-specific autophagy-related gene 5 (Atg5) knockout (KO) mice. Liver regeneration was severely impaired by 70% PHx, with a reduction in postoperative mitosis, but a compensating increase in hepatocyte size. PHx induced intracellular adenosine triphosphate and beta-oxidation reduction as well as injured cellular mitochondria. Furthermore, PHx in Atg5 KO mice enhanced hepatic accumulation of p62 and ubiquitinated proteins. These results indicated that reorganization of intracellular proteins and organelles during autophagy was impaired in the regenerating liver of these mice. Up-regulation of p21 was associated with hepatocyte senescence, senescence-associated b-galactosidase expression, irreversible growth arrest, and secretion of senescence-associated molecules, including interleukin (IL)-6 and IL-8.

Research Products

• [Journal Article] Skeletal muscle area correlates with body surface area in healthy adults (2014)
  • Author(s): Yoshizumi T, Shirabe K, Nakagawara H, Ikegami T, Harimoto N, Toshima T, Yamashita Y, Ikeda T, Soejima Y, Maehara Y.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 313-8
  • DOI: 10.1111/hepr.12119
• [Journal Article] Decreased immunoglobulin G levels after living donor liver transplantation is a risk factor for bacterial infection and sepsis (2014)
  • Author(s): Yoshizumi T, Shirabe K, Ikegami T, Yamashita N, Mano Y, Yoshiya S, Matono R, Harimoto N, Uchiyama H, Toshima T, Maehara Y.
  • Journal Title: Transpl Infect Dis. Volume: 16(2) Pages: 225-31
  • DOI: 10.1111/tid.12188
• [Journal Article] Autophagy enhances hepatocellular carcinoma progression by activation of mitochondrialβ-oxidation (2014)
  • Author(s): Toshima T, Shirabe K, Matsumoto Y, Yoshiya S, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Maehara Y.
  • Journal Title: J Gastroenterol Volume: 49(5) Pages: 907-16
  • DOI: 10.1007/s00535-013-0835-9
• [Journal Article] Suppression of autophagy during liver regeneration impairs energy charge and hepatocyte senescence in mice (2014)
  • Author(s): Toshima T, Shirabe K, Fukuhara T, Ikegami T, Yoshizumi T, Soejima Y, Ikeda T, Okano S, Maehara Y.
  • Journal Title: Hepatology Volume: (Epub ahead of print)
  • DOI: 10.1002/hep.27140
• [Journal Article] Re-evaluation of predictive score for 6-month graft survival in living donor liver transplantation in modern era (2013)
  • Author(s): Yoshizumi T, Ikegami T, Bekki Y, Ninomiya M, Uchiyama H, Iguchi T, Yamashita Y, Kawanaka H, Shirabe K, Maehara Y.
  • Journal Title: Liver Transpl Volume: (Epub ahead of print)
  • DOI: 10.1002/lt.23804
• [Journal Article] Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma (2013)
  • Author(s): Yoshizumi T, Ikegami T, Toshima T, Harimoto N, Uchiyama H, Soejima Y, Yamashita Y, Shirabe K, Maehara Y.
  • Journal Title: Transplant Proc. Volume: 45 Pages: 3310-3
  • DOI: 10.1016/j.transproceed.2013.05.001
• [Journal Article] Impact of tumor size, number of tumors and neutrophil-to-lymphocyte ratio in liver transplantation for recurrent hepatocellular carcinoma (2013)
  • Author(s): Yoshizumi T, Ikegami T, Yoshiya S, Motomura T, Mano Y, Muto J, Ikeda T, Soejima Y, Shirabe K, Maehara Y.
  • Journal Title: Hepatol Res. Volume: 43(7) Pages: 709-16
  • DOI: 10.1111/hepr.12016
• [Journal Article] Impact of human T-cell leukemia virus type 1 in living donor liver transplantation (2012)
  • Author(s): Yoshizumi T, Shirabe K, Ikegami T, Kayashima H, Yamahita N, Morita K, Masuda T, Hashimoto N, Taketomi A, Soejima Y, Maehara Y.
  • Journal Title: Am J Transplant Volume: 12(6) Pages: 1479-85
  • DOI: 10.1111/j.1600-6143.2012.04037.x
• [Journal Article] Risk factors that increase Mortality after living donor liver transplantation (2012)
  • Author(s): Yoshizumi T, Shirabe K, Taketomi A, Uchiyama H, Harada N, Ijichi H, Yoshimatsu M, Ikegami T, Soejima Y, Maehara Y.
  • Journal Title: Transplantation Volume: 93 Pages: 93-8
  • DOI: 10.1097/TP.0b013e318238dacd
• [Presentation] 肝再生におけるオートファジーの生物学的意義
  • Author(s): 戸島剛男, 調憲, 吉屋匠平, 武藤純, 的野る美, 間野洋平, 池上徹, 吉住朋晴, 前原喜彦
  • Organizer: 日本消化器外科学会総会67回
• [Presentation] 肝再生の機序解明と臨床への応用肝再生におけるオートファジーの生物学的意義
  • Author(s): 戸島剛男, 調憲, 吉屋匠平, 播本憲史, 山下洋市, 池上徹, 内山秀昭, 吉住朋晴, 副島雄二, 前原喜彦
  • Organizer: 日本外科学会総会114回
• [Presentation] 肝分化/再生/幹細胞肝再生におけるオートファジーの生物学的意義
  • Author(s): 戸島剛男, 調憲, 吉屋匠平, 武藤純, 的野る美, 間野洋平, 森田和豊, 萱島寛人, 池上徹, 吉住朋晴, 前原喜彦
  • Organizer: 肝臓学会総会49回
• [Presentation] 侵襲に対する生体反応とその制御肝再生におけるオートファジーの意義
  • Author(s): 戸島剛男, 調憲, 武冨紹信, 間野洋平, 武藤純, 的野る美, 吉屋匠平, 森田和豊, 萱島寛人, 池上徹, 吉住朋晴, 前原喜彦
  • Organizer: 日本外科学会総会113回
• [Presentation] 肝細胞癌進展におけるオートファジーの意義
  • Author(s): 戸島剛男, 調憲, 武冨紹信, 本村貴志, 間野洋平, 武藤純, 的野る美, 吉屋匠平, 森田和豊, 萱島寛人, 池上徹, 吉住朋晴, 前原喜彦
  • Organizer: 日本癌治療学会総会51回