2020 Fiscal Year Final Research Report
Analysis of downstream effectors of PDGF signaling to identify novel therapeutic targets in pulmonary hypertension
| Project/Area Number |
18K08128
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| 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) |
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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)
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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 肺高血圧 / シグナル伝達 / 転写因子 / 肺動脈平滑筋細胞 |
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| 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.
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| Free Research Field |
肺高血圧
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| 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．
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