2015 Fiscal Year Final Research Report
The generation of a new animal model of systemic sclerosis by focusing on environmental factors
Project/Area Number |
26670520
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Dermatology
|
Research Institution | The University of Tokyo |
Principal Investigator |
Sato Shinichi 東京大学, 医学部附属病院, 教授 (20215792)
|
Co-Investigator(Kenkyū-buntansha) |
Asano Yoshihide 東京大学, 医学部附属病院皮膚科, 准教授 (60313029)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Keywords | 全身性強皮症 / 転写因子 / エピジェネティックス / 線維化 / 血管障害 / 免疫異常 |
Outline of Final Research Achievements |
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by three cardinal pathological features, including immune abnormalities/inflammation, vasculopathy, and fibrosis. Although the pathogenesis of SSc still remains unknown, it is generally accepted that environmental factors play a critical role in the development of this disease in genetically predisposed individuals. In SSc dermal fibroblasts, two transcription factors, Fli1 and KLF5, are epigenetically suppressed, suggesting that the downregulation of these molecules is likely to be predisposing factors of SSc. Of note, mice with heterozygous deletion of Fli1 and Klf5 spontaneously developed the three cardinal pathological features of SSc, strictly recapitulating the sequential pathological process (initiating with immune abnormalities, followed by vasculopathy, and eventually resulting in tissue fibrosis). Further studies with this murine model would provide a useful clue to understand SSc pathogenesis.
|
Free Research Field |
全身性強皮症
|