Calcium-sensing receptor as a novel drug target for pulmonary hypertension
| Project/Area Number |
17K08320
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pharmacology in pharmacy
|
|---|
| Research Institution | Aichi Medical University |
|---|
Principal Investigator |
Yamamra Aya 愛知医科大学, 医学部, 講師 (40633219)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 肺高血圧症 / カルシウム感受性受容体 / 血管 / リモデリング / 平滑筋 / PDGFシグナル / カルシウムシグナル / 肺動脈 / 血小板由来成長因子 / PDGF受容体 / リン酸化 / PDGF / 薬理学 / 生理学 / 薬学 / 循環器・高血圧 / トランスレーショナルリサーチ |
|---|
| Outline of Final Research Achievements |
Pulmonary arterial hypertension (PAH) is a progressive and fatal disease of the pulmonary artery. We previously reported that the calcium-sensing receptor (CaSR) was upregulated in pulmonary arterial smooth muscle cells (PASMCs) from idiopathic pulmonary arterial hypertension (IPAH) patients. In this study, we examined involvement of platelet-derived growth factor (PDGF) on CaSR expression. The expression of PDGF receptors was stronger in IPAH-PASMCs than in normal-PASMCs.The PDGF-induced CaSR upregulation was attenuated by the siRNA knockdown of PDGF receptors.These results suggest that enhanced PDGF signaling is involved in the CaSR upregulation, leading excessive PASMC proliferation and vascular remodeling in IPAH patients. The linkage between CaSR and PDGF signals is a novel pathophysiological mechanism contributing to the development of PAH.
|
| Academic Significance and Societal Importance of the Research Achievements |
肺動脈性肺高血圧症（PAH）は、持続的に肺動脈圧が上昇する進行性かつ難治性の血管疾患である。近年、PAHの予後は、改善しつつあるが、特徴的な症状がないため、右心不全を起こして初めて診断される症例が多い。PAHの薬剤は、肺血管を拡張させて、肺動脈圧を降下させるものである。PAH病態が悪化するにつれて生じる肺血管壁の細胞増殖（肺血管リモデリング）を抑える根本的な薬剤は実用化されていないのが現状である。そのため、本研究で明らかにした、PAH患者で亢進したPDGFシグナルがCaSR発現を亢進させ、病態を悪化させるメカニズムは新規治療薬の開発において有益な情報になると期待している。
|
Report
(4 results)
Research Products
(40 results)
-
-
-
[Journal Article] MicroRNA-mediated downregulation of K+ channels in pulmonary arterial hypertension2020
Author(s)
Babicheva Aleksandra、Ayon Ramon J.、Zhao Tengteng、Ek Vitorin Jose F.、Pohl Nicole M.、Yamamura Aya、Yamamura Hisao、Quinton Brooke A.、Ba Manqing、Wu Linda、Ravellette Keeley S.、Rahimi Shamin、Balistrieri Francesca、Harrington Angela、Vanderpool Rebecca R.、Thistlethwaite Patricia A.、Makino Ayako、Yuan Jason X.-J.
-
Journal Title
American Journal of Physiology-Lung Cellular and Molecular Physiology
Volume: 318
Issue: 1
Pages: L10-L26
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
-
-
[Journal Article] Nicotinamide phosphoribosyltransferase promotes pulmonary vascular remodeling and is a therapeutic target in pulmonary arterial hypertension.2017
Author(s)
Chen J, Sysol JR, Singla S, Zhao S, Yamamura A, Valdez-Jasso D, Abbasi T, Shioura KM, Sahni S, Reddy V, Sridhar A, Gao H, Torres J, Camp SM, Tang H, Ye SQ, Comhair S, Dweik R, Hassoun P, Yuan JX, Garcia JG, Machado RF.
-
Journal Title
Circulation
Volume: 135(16)
Issue: 16
Pages: 1532-1546
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
