| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Outline of Final Research Achievements |
Pulmonary arterial hypertension (PAH) is a poor prognostic complication of connective tissue disease (CTD). Increased expression of endothelin-1 (ET-1) is of particular interest for its pathogenic role in PAH. We previously identified non-synonymous single nucleotide polymorphisms (SNPs) of HIF3A gene in the patients with systemic sclerosis (SSc) associated with PAH and demonstrated that ET-1 mRNA is induced by overexpression of HIF-3α carrying the SNPs (SNP-HIF3α) even under normoxic condition. In this study, we aim to further investigate the pathophysiological roles of SNP-HIF3α in ET-1 regulation with respect to PAH. We found SSc-PAH related SNP-HIF3α is a potent transcriptional activator of ET-1 gene. Upregulated ET-1 by SNP-HIF3αcaused enhancement of proliferation and migration of pulmonary artery smooth muscle cells. In conclusion, SNP-HIF3α might paly a role in dysregulation of pulmonary arterial remodeling and contribute to pathogenesis of PAH in SSc.
|
