Possible mechanism of ballooned hepatocyte formation in non-alcoholic steatohepatitis

• Project/Area Number: 16K21307
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology; Metabolomics
• Research Institution: Iwate Medical University
• Principal Investigator: Kakisaka Keisuke 岩手医科大学, 医学部, 助教 (40583563)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 非アルコール性脂肪肝炎 / NASH / 風船様肝細胞 / Ballooned hepatocyte / Hepatocyte ballooning / Autophagy / Fibrosis / 肝線維化 / Ballooning / Rubicon / カスパーゼ９ / オートファジー / 内科 / シグナル伝達

Outline of Final Research Achievements

The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased. Non-alcoholic steatohepatitis (NASH) shows progression of liver fibrosis in NAFLD. NASH os characterized by presence of ballooned hepatocyte. We revealed that signaling of cell death and impaired autophagic process were associated with morphological and biochemical similarity of ballooned hepatocyte. We also found the presence of ballooned hepatocytes was a risk factor for the progression of liver fibrosis in clinical study. The present project demonstrated that ballooned hepatocyte might be therapeutic target of NASH.

Research Products

• [Journal Article] Evaluation of ballooned hepatocytes as a risk factor for future progression of fibrosis in patients with non-alcoholic fatty liver disease (2018)
  • Author(s): Kakisaka Keisuke、Suzuki Yuji、Fujiwara Yudai、Abe Tamami、Yonezawa Miki、Kuroda Hidekatsu、Ishida Kazuyuki、Sugai Tamotsu、Takikawa Yasuhiro
  • Journal Title: Journal of Gastroenterology Volume: NA Issue: 12 Pages: 1285-1291
  • DOI: 10.1007/s00535-018-1468-9
  • Peer Reviewed / Open Access
• [Journal Article] Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure. (2017)
  • Author(s): Kakisaka Keisuke, Kataoka Kojiro, Suzuki Yuji, Kuroda Hidekatsu, Takikawa Yasuhiro.
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 8 Pages: 977-985
  • DOI: 10.1007/s00535-017-1306-5
  • NAID: 120006313047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] c-Jun N-terminal kinase-mediated Rubicon expression enhances hepatocyte lipoapoptosis and promotes (2016)
  • Author(s): Suzuki A, Kakisaka K, Suzuki Y, Wang T, Takikawa Y.
  • Journal Title: World J Gastroenterol. Volume: 22 Issue: 28 Pages: 6509-19
  • DOI: 10.3748/wjg.v22.i28.6509
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Reversible sclerosing cholangitis with ulcerative colitis. (2016)
  • Author(s): Kakisaka K, Ishida K, Kataoka K, Suzuki Y, Yanai S, Kuroda H, Sugai T, Matsumoto T, Takikawa Y
  • Journal Title: Pathol Int. Volume: 66 Issue: 7 Pages: 404-408
  • DOI: 10.1111/pin.12427
  • NAID: 120006666415
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Ｃａｓｐａｓｅ９はオートファジーを抑制するＲｕｂｉｃｏｎを分解し、肝細胞のＢａｌｌｏｏｎｉｎｇを抑制する (2016)
  • Author(s): 柿坂啓介、鈴木彰子、滝川康裕
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ幕張
  • Year and Date: 2016-05-19
• [Presentation] 非アルコール性脂肪性肝疾患におけるオートファジー抑制機構とBallooned hepatocyte形成についての基礎的検討 (2016)
  • Author(s): 柿坂啓介、鈴木彰子、滝川康裕
  • Organizer: 広島肝臓プロジェクト
  • Place of Presentation: ホテルグランヴィア広島
• [Remarks] 岩手医科大学消化器内科肝臓分野ホームページ 研究内容
  • URL: http://gastro-hepatol.iwate-med.ac.jp/kouza/kenkyu/index.html