• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of molecular mechanisms involved in progression to jaundice and liver failure in primary biliary cholangitis

Research Project

Project/Area Number 15K19357
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionDepartment of Clinical Research, National Hospital Organization Nagasaki Medical Center

Principal Investigator

AIBA YOSHIHIRO  独立行政法人国立病院機構(長崎医療センター臨床研究センター), 臨床研究センター, 研究員 (70450955)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords原発性胆汁性胆管炎 / 原発性胆汁性肝硬変 / GWAS / CTSZ / カテプシン / 重症化機構 / 疾患関連遺伝子 / 肝不全
Outline of Final Research Achievements

We identified NELFCD/CTSZ as loci associated with progression to jaundice and liver failure (end-stage) in primary biliary cholangitis (PBC).Serum CTSZ levels were significantly higher in end-stage than other stages (early-stage or late-stage) in PBC. The levels of CTSZ were significantly correlated with those of aspartate transaminase, total bilirubin, platelet count, and albumin in the blood of PBC. The levels of CTSZ protein in hepatocytes were increased with the progression of PBC. In end-stage PBC, the localization of CTSZ was translocated from peri-bile canalicular region to inner cytoplasmic region of hepatocytes, where a part of CTSZ was not co-localized with endsomal/lysosomal vesicles. Chloroquine and amino acid starvation enhanced cell death in CTSZ transfected HuH7. These results indicated that the increased expression and altered localization of CTSZ might be implicated in the progression of PBC via cell death.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population2017

    • Author(s)
      Kawashima M, Honda M, Nakamura M. et al.
    • Journal Title

      Hum Mol Genet.

      Volume: 26 Issue: 3 Pages: 650

    • DOI

      10.1093/hmg/ddw406

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Disease susceptibility genes shared by primary biliary cirrhosis and Crohn’s disease in the Japanese population2015

    • Author(s)
      Yoshihiro Aiba, Keiko Yamazaki, Nao Nishida, Minae Kawashima, Yuki Hitomi, Hitomi Nakamura, Atsumasa Komori, Yuta Fuyuno, Atsushi Takahashi, Takaaki Kawaguchi, Masakazu Takazoe, Yasuo Suzuki, Satoshi Motoya Toshiyuki Matsui Motohiro Esaki, Takayuki Matsumoto, Michiaki Kubo, Katsushi Tokunaga, Minoru Nakamura
    • Journal Title

      Journal of Human Genetics

      Volume: 印刷中 Issue: 9 Pages: 525-531

    • DOI

      10.1038/jhg.2015.59

    • NAID

      40020589506

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1.2015

    • Author(s)
      Hitomi Y, Kawashima M, Aiba Y, Nishida N, Matsuhashi M, Okazaki H, Nakamura M, Tokunaga K
    • Journal Title

      Human Genetics

      Volume: 印刷中 Issue: 7 Pages: 737-747

    • DOI

      10.1007/s00439-015-1556-3

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Cathepsin Z variants are associated with progression to end-stage hepatic failure in Japanese patients with primary biliary cholangitis2017

    • Author(s)
      Nao Nishida, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Hitomi Nakamura, Noriyo Yamashiki, Tomohiro Tanaka, Sumito Tamura, Akira Mori, Shintaro Yagi, Yuji Soejima, Ken Shirabe, Atsushi Tanaka, Kenichi Harada, Shinji Shimoda Atsumasa Komori, Katsushi Tokunaga, Minoru Nakamura et al.
    • Organizer
      ヨーロッパ肝臓学会総会
    • Place of Presentation
      アムステルダム
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日本人原発性胆汁性肝硬変における黄疸・肝不全型進行関連遺伝子の同定2016

    • Author(s)
      相葉佳洋、西田奈央、中村稔
    • 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
    • Related Report
      2016 Annual Research Report
  • [Presentation] 原発性胆汁性肝硬変におけるTL1Aの役割2015

    • Author(s)
      相葉佳洋、小森敦正、中村 稔
    • Organizer
      第41回日本肝臓学会西部会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 日本人原発性胆汁性肝硬変の新規疾患感受性遺伝子PRKCB, ETS1 の同定2015

    • Author(s)
      相葉佳洋、川嶋美苗、 西田奈央、 人見祐基、小森敦正、 茶山一彰、安波道郎、徳永勝士、 中村 稔
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本ホテル日航
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] Shared Disease-Susceptibility genes between primary biliary cirrhosis and Crohn's disease in the Japanese population2015

    • Author(s)
      Yoshihiro Aiba, Keiko Yamazaki,Nao Nishida, Minae Kawashima, Yuki Hitomi, Atsumasa Komori, Michiaki Kubo, Katsushi Tokunaga, Minoru Nakamura
    • Organizer
      ヨーロッパ肝臓学会総会
    • Place of Presentation
      ウィーン
    • Year and Date
      2015-04-22
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2021-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi