Analysis of downstream effectors of PDGF signaling to identify novel therapeutic targets in pulmonary hypertension
| Project/Area Number |
18K08128
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53020:Cardiology-related
|
|---|
| Research Institution | 独立行政法人国立病院機構岡山医療センター(臨床研究部) |
|---|
Principal Investigator |
Matsubara Hiromi 独立行政法人国立病院機構岡山医療センター(臨床研究部), 独立行政法人国立病院機構 岡山医療センター(臨床研究部), 副院長 (70252955)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
小川 愛子 独立行政法人国立病院機構岡山医療センター(臨床研究部), 独立行政法人国立病院機構 岡山医療センター(臨床研究部), 分子病態研究室長 (40572748)
狩野 光伸 岡山大学, ヘルスシステム統合科学研究科, 教授 (80447383)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 肺高血圧 / シグナル伝達 / 転写因子 / 肺動脈平滑筋細胞 / 微小血管モデル |
|---|
| Outline of Final Research Achievements |
We studied the role of the transcription factor distal-less homeobox 1 (DLX1) in the proliferation of pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Knockdown of DLX1 expression resulted in a marked reduction of PASMC proliferation at baseline as well as in the presence of platelet-derived growth factor (PDGF) ligands. Microarray analyses implicated reduced expression of integrin subunits as a mechanism underlying reduced PASMC proliferation upon DLX1 knockdown. Indeed, knockdown of the integrin subunit resulted in a reduced PASMC proliferation at baseline and in the presence of PDGF ligands. Furthermore, the respective ligand of the integrin subunit was elevated in the sera of PH patients compared to healthy controls. Altogether, our results suggest that DLX1, downstream of PDGF signaling, modulates integrin expression to promote PASMC proliferation in the pathogenesis of PH.
|
| Academic Significance and Societal Importance of the Research Achievements |
難病である肺高血圧症に対する治療薬が近年複数開発されてきたが，治療成績の改善はまだ不十分である．肺高血圧症の悪化に重要な役割を果たすPDGF経路を効果的に抑制する標的分子の候補を明らかにすることができたため，この分子を特異的に抑制する治療薬を開発することで，肺高血圧症の治療成績が改善できる可能性が示された．
|
Report
(4 results)
Research Products
(48 results)
-
-
-
-
-
-
-
[Journal Article] Sex-specific differences in chronic thromboembolic pulmonary hypertension. Results from the European CTEPH registry.2020
Author(s)
Barco S, Klok FA, Konstantinides SV, Dartevelle P, Fadel E, Jenkins D, Kim NH, Madani M, Matsubara H, Mayer E, Pepke-Zaba J, Simonneau G, Delcroix M, Lang IM.
-
Journal Title
J Thromb Haemost
Volume: 18
Issue: 1
Pages: 151-161
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] Chronic thromboembolic pulmonary hypertension in Austria and Japan2019
Author(s)
Chausheva Stella、Naito Akira、Ogawa Aiko、Seidl Veronika、Winter Max-Paul、Sharma Smriti、Sadushi-Kolici Roela、Campean Ioana-Alexandra、Taghavi Shahroukh、Moser Bernhard、Klepetko Walter、Ishida Keiichi、Matsubara Hiromi、Sakao Seiichiro、Lang Irene M.
-
Journal Title
The Journal of Thoracic and Cardiovascular Surgery
Volume: 印刷中
Issue: 2
Pages: 604-614
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] Chronic thromboembolic pulmonary hypertension2019
Author(s)
Kim Nick H.、Delcroix Marion、Jais Xavier、Madani Michael M.、Matsubara Hiromi、Mayer Eckhard、Ogo Takeshi、Tapson Victor F.、Ghofrani Hossein-Ardeschir、Jenkins David P.
-
Journal Title
European Respiratory Journal
Volume: 53
Issue: 1
Pages: 1801915-1801915
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
