Role of IPAS/HIF-3alpha-mediated signals in the pathophysiology of pulmonary hypertension associated with connective tissue disease
| Project/Area Number |
26461456
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Collagenous pathology/Allergology
|
|---|
| Research Institution | Asahikawa Medical College |
|---|
Principal Investigator |
Makino Yuichi 旭川医科大学, 医学部, 准教授 (90345033)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
川口 鎮司 東京女子医科大学, 医学部, 准教授 (90297549)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| 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)
|
|---|
| Keywords | 一塩基多型 / エンドセリン1 / 低酸素 / 膠原病 / 肺高血圧症 / HIF / エンドセリン１ / HIF-3a |
|---|
| 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.
|
Report
(4 results)
Research Products
(4 results)
-
-
-
[Presentation] Pulmonary arterial hypertension-associated single nucleotide polymorphisms of hypoxia-inducible factor-3α gene cause constitutive activation of the endothelin-1 gene promoter.2015
Author(s)
Mizumoto K, Takatori K, Takatori S, Yoshimoto R, Eguchi K, Fujishiro D, Kodama S, Kobayashi A, Okamoto K, Kawaguchi Y,Haneda M, and Makino Y
Organizer
American College of Rheumatology Annual Meeting,2015
Place of Presentation
San Francisco, USA
Year and Date
2015-11-07
Related Report
Int'l Joint Research
-
