ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 1912

Glycyrrhizin Ameliorates Fibrosis, Vasculopathy, and Immune Abnormalities in Animal Models of Systemic Sclerosis

Takashi Yamashita1, Yoshihide Asano2, Takashi Taniguchi1, Ryosuke Saigusa3, Kouki Nakamura1, Syunnsuke Miura2, Tetsuo Toyama1, Takehiro Takahashi1, Yohei Ichimura1, Ayumi Yoshizaki1, Maria Trojanowska4 and Shinichi Sato1, 1Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan, 2University of Tokyo Graduate School of Medicine, Tokyo, Japan, 37-3-1 Hongo, Bunkyo-ku, University of Tokyo Graduate School of Medicine, Tokyo, Japan, 4Arthritis Center, Boston University, Arthritis Center, Boston, MA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Scleroderma

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Monday, November 9, 2015

Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:  Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and fibrosis of the skin and various internal organs. Glycyrrhizin, a triterpenoid saponin glycoside from the roots of licorice, is a clinically approved for the treatment of chronic hepatic diseases and itching dermatitis and has also been used for Kampo in the Orient from ancient times. Importantly, glycyrrhizin has been shown to modulate the pathological processes of fibrosis, inflammation, and vasculopathy in some experimental disease models. Based on these backgrounds, we investigated the effect of glycyrrhizin on the three cardinal pathological features of SSc, including tissue fibrosis, inflammation, and vasculopathy, utilizing bleomycin (BLM)-treated mice recapitulating the fibrotic and inflammatory aspects of SSc and endothelial cell-specific Fli1 knockout (Fli1ECKO) mice mimicking SSc vasculopathy.

Methods: Wild type C57BL/6 mice were subcutaneously injected with BLM or phosphate buffered saline (PBS) for the indicated period of time together with daily intraperitoneal injection of glycyrrhizin (30mg/kg) or PBS. mRNA and/or protein levels of target molecules were determined by quantitative reverse transcription-PCR, immunostaining, and/or immunoblotting in the skin samples and cultivated cells. Th1/Th2/Th17 polarization of immune response and macrophages polarization were evaluated by flow cytometry. Vascular permeability was evaluated by Evans blue dye injection in Fli1ECKO mice.

Results: Glycyrrhizin significantly ameliorated dermal thickness and collagen contents and decreased the number of myofibroblasts in BLM-treated mice. Consistent with these findings, glycyrrhizin significantly suppressed mRNA levels of the Col1a1, Col1a2, and Col3a1 genes, while not those of the Ctgf and Tgfb genes in the lesional skin of BLM-treated mice. Since mRNA levels of the Thbs1 gene, encoding thrombospondin 1 which activates latent form of TGF-Β, were significantly reduced under the same condition, glycyrrhizin is likely to prevent the development of BLM-induced dermal fibrosis at least partially by blocking autocrine TGF-Β signaling in dermal fibroblasts. As for the expression profiles of cytokines and chemokines, the reduction of IL-4 and IL-6 was noted in the lesional skin of BLM-treated mice administered glycyrrhizin. Consistently, glycyrrhizin attenuated the BLM-dependent induction of Th2 cells in draining lymph nodes and spleen, partially contributing to the prevention of BLM-induced dermal fibrosis. Relevant to this finding, the expression levels of M2 macrophage markers were decreased by glycyrrhizin in the lesional skin of BLM-treated mice. With respect to the pathological vascular aspects, glycyrrhizin prevented the BLM-dependent induction of endothelial-to-mesenchymal transition, also associated with the reduction of dermal fibrosis by this agent, and improved the leaky vascular phenotype of Fli1ECKO mice.

Conclusion: Glycyrrhizin has potential preventive and/or therapeutic effects on the pathological dermal fibrosis and vasculopathy similar to SSc by acting on fibroblasts, endothelial cells, and immune cells.


Disclosure: T. Yamashita, None; Y. Asano, Koki Co., 2; T. Taniguchi, None; R. Saigusa, None; K. Nakamura, None; S. Miura, None; T. Toyama, None; T. Takahashi, None; Y. Ichimura, None; A. Yoshizaki, None; M. Trojanowska, None; S. Sato, None.

To cite this abstract in AMA style:

Yamashita T, Asano Y, Taniguchi T, Saigusa R, Nakamura K, Miura S, Toyama T, Takahashi T, Ichimura Y, Yoshizaki A, Trojanowska M, Sato S. Glycyrrhizin Ameliorates Fibrosis, Vasculopathy, and Immune Abnormalities in Animal Models of Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/glycyrrhizin-ameliorates-fibrosis-vasculopathy-and-immune-abnormalities-in-animal-models-of-systemic-sclerosis/. Accessed March 3, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/glycyrrhizin-ameliorates-fibrosis-vasculopathy-and-immune-abnormalities-in-animal-models-of-systemic-sclerosis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.