| Project/Area Number |
23791256
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2011 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 全身性強皮症 / 血管障害 / Fli1 / エンドセリン / ボセンタン / 創傷治癒 / 国際情報交流 アメリカ合衆国 |
|---|
| Research Abstract |
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by initial vascular injuries and resultant fibrosis of skin and certain internal organs. Although the pathogenesis of SSc still remains unknown, recent studies have demonstrated that endothelins play a crucial role in the development of vasculopathy and fibrosis associated with SSc. Consistently, we recently showed that Fli1 deficiency is closely linked to the activation of fibroblasts and endothelial cells in SSc and a dual endothelin receptor antagonist, bosentan, reverses the pro-fibrotic phenotype of SSc dermal fibroblasts by increasing the transcriptional activity of Fli1. Based on these findings, we herein investigated the impact of bosentan on SSc vasculopathy using endothelia cell-specific Fli1 knockout mice, which mimic the morphological and functional abnormalities of SSc vasculopathy. A series of studies revealed that bosentan reverses Fli1 deficiency-dependent vasculopathy in these mice by increasing transcriptional activity of Fli1, suggesting that a similar mechanism potentially underpins the clinical efficacy of bosentan for SSc vasculopathy.
|
