The development of new therapies targeting the three cardinal pathological processes of systemic sclerosis

Research Project

Project/Area Number	16K15511
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Collagenous pathology/Allergology
Research Institution	The University of Tokyo
Principal Investigator	Sato Shinichi 東京大学, 医学部附属病院, 教授 (20215792)
Project Period (FY)	2016-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	全身性強皮症 / 動物モデル / 線維化 / 血管障害 / 免疫異常 / Fli1 / ブレオマイシン / シクロホスファミド / 脈管形成 / グリチルリチン / 炎症 / 膠原病学
Outline of Final Research Achievements	Systemic sclerosis (SSc) is a multisystem autoimmune disease chracterized by vasculopathy and fibrosis of the skin and various internal organs. We recently established a new experimental system in which the three pathological features of SSc, such as immune abnormality, vasculopathy, and tissue fibrosis, can be separately assessed by using endothelial cell-specific Fli1 knockout mice, which mimic SSc vasculopathy, and bleomycin-treated mice, which resemble inflammation and tissue fibrosis of SSc.In this study, we identified the mechanisms by which glycyrrhizin and cyclophosphamide affect the developmental process of SSc by using this experimental system. At the time of writing, glycyrrhizin is applied for a patent, and we are conducting a prospective clinical study to evaluate the efficacy of glycyrrhizin on SSc vasculopathy.