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

Development of a new treatment for primary sclerosing cholangitis with indigo naturalis

Research Project

Project/Area Number 20K17062
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKeio University

Principal Investigator

Taniki Nobuhito  慶應義塾大学, 医学部(信濃町), 講師 (20627129)

Project Period (FY) 2020-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsAhR / 原発性硬化性胆管炎 / 青黛
Outline of Research at the Start

原発性硬化性胆管炎(PSC, Primary Sclerosing Cholangilitis)の新規治療の開発が求められている。PSC患者ではしばしば潰瘍性大腸炎(UC, ulcerative colitis)を合併し、PSCの病態形成にUCが深く関わるとされる。本研究では、UCに対して有効な生薬である青黛のPSCに対する有効性を検証する。また、青黛はインジゴなどのAryl hydrocarbon receptor (AhR)リガンドを主成分とすることから、AhRがPSCの病態形成に与える役割を、免疫細胞、上皮細胞、腸内細菌叢およびその相互作用を細胞生物学的に理解することを目指す。

Outline of Final Research Achievements

Currently, no cure or effective treatments for primary sclerosing cholangitis (PSC) exist, and development of new treatment is on demand. Inflammatory bowel disease (IBD) and PSC are closely associated disease. We previously reported efficacy of aryl hydrocarbon receptor (AhR) ligand-containing biopharmaceutica agent, indigo naturalis (IN) in inducing a clinical response in patients with ulcerative colitis in a randomized, placebo-controlled trial. In the current study, we analyzed the efficacy of IN for patients with PSC. We found IN to be effective in reducing cholangitis of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced and MDR2 KO PSC model mouse in an AhR-dependent manner. In the future, we aim to clarify the effects of IN and AhR on the pathogenesis of PSC and to disseminate IN as drug discovery seeds for PSC.

Academic Significance and Societal Importance of the Research Achievements

PSCは肝内外胆管のびまん性狭窄を生じる慢性炎症性疾患であり、有効な治療法が確立されておらず、進行例では肝移植が唯一の救命法である。肝移植に関しては脳死肝移植ドナーの少ない本邦では生体肝移植が主に行われているが、生体肝移植後のPSC再発率が高いことが問題となっており、新たな治療法の開発が求められている。本研究ではAhRリガンドをPSCに対する新たな創薬シーズとして臨床応用に展開するための基盤的研究を行う。本研究ではすでに青黛がAhR依存的にin vivoマウス硬化性胆管炎における病態形成の抑制に寄与することを見出しており、PSCに対する新たな治療を開発するための画期的な知見と言える。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (2 results)

All 2022 2020

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results)

  • [Journal Article] Th17 cells in the liver: balancing autoimmunity and pathogen defense2022

    • Author(s)
      Taniki Nobuhito、Nakamoto Nobuhiro、Chu Po-Sung、Ichikawa Masataka、Teratani Toshiaki、Kanai Takanori
    • Journal Title

      Seminars in Immunopathology

      Volume: - Issue: 4 Pages: 509-526

    • DOI

      10.1007/s00281-022-00917-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The liver-brain-gut neural arc maintains the Treg cell niche in the gut2020

    • Author(s)
      Teratani T, Mikami Y, Nakamoto N, Suzuki T, Harada Y, Okabayashi K, Hagihara Y, Taniki N, Kohno K, Sibata S, Miyamoto K, Ishigame H, Chu Po-Sung, Sujino T, Suda W, Hattori M, Matsui M, Okada T, Okano H, Inoue M, Yada T, Kitagawa Y, Yoshimura A, Tanida M, Tsuda M, Iwasaki Y, Kanai T.
    • Journal Title

      Nature

      Volume: 585 Issue: 7826 Pages: 591-596

    • DOI

      10.1038/s41586-020-2425-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2020-04-28   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi