Mechanism underlying upregulation of calcium-sensing receptor in pulmonary hypertension

• Project/Area Number: 15K18881
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Kinjo Gakuin University
• Principal Investigator: YAMAMURA Aya 金城学院大学, 薬学部, 助教 (40633219)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肺高血圧症 / カルシウム感受性受容体 / イオンチャネル / 肺動脈 / 平滑筋 / カルシウムシグナル / 細胞増殖 / リモデリング / ホスホジエステラーゼ / 肺高血圧 / TRPC6チャネル

Outline of Final Research Achievements

Pulmonary arterial hypertension is an intractable disease that pulmonary arterial pressure chronically increases due to vascular impairment. We found that upregulation of calcium-sensing receptor in pulmonary arterial smooth muscle cells is involved in pathogenesis of pulmonary arterial hypertension. In this study, we showed that functional coupling of calcium-sensing receptor with TRPC6 channel and usefulness of calcium-sensing receptor antagonists for pulmonary arterial hypertension. Our findings provide novel therapeutic strategies for pulmonary arterial hypertension.

Research Products

• [Int'l Joint Research] アリゾナ大学/イリノイ大学シカゴ校(米国)
• [Int'l Joint Research] アリゾナ大学/イリノイ大学シカゴ校(米国)
• [Journal Article] Capsaicin-induced Ca2+ signaling is enhanced via upregulated TRPV1 channels in pulmonary artery smooth muscle cells from patients with idiopathic PAH. (2017)
  • Author(s): Song S, Ayon RJ, Yamamura A, Yamamura H, Dash S, Babicheva A, Tang H, Sun X, Cordery AG, Khalpey Z, Black SM, Desai AA, Rischard F, McDermott KM, Garcia JG, Makino A, Yuan JX.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: 312(3) Issue: 3 Pages: L309-L325
  • DOI: 10.1152/ajplung.00357.2016
  • 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: 10.1161/circulationaha.116.024557
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 肺高血圧症とカルシウム感受性受容体 (2017)
  • Author(s): 山村彩
  • Journal Title: Medical Science Digest Volume: 43(2) Pages: 112-113
• [Journal Article] 肺高血圧症における平滑筋細胞のカルシウムチャネルの種類と役割 (2017)
  • Author(s): 山村寿男, 山村彩
  • Journal Title: Pulmonary Hypertension Update Volume: 印刷中
• [Journal Article] Molecular Mechanism of Dihydropyridine Ca²⁺ Channel Blockers in Pulmonary Hypertension (2016)
  • Author(s): 山村彩
  • Journal Title: YAKUGAKU ZASSHI Volume: 136 Issue: 10 Pages: 1373-1377
  • DOI: 10.1248/yakushi.16-00086
  • NAID: 130005598012
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2016-10-01
  • Open Access
• [Journal Article] Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension. (2016)
  • Author(s): Tang H, Yamamura A, Yamamura H, Song S, Fraidenburg DR, Chen J, Gu Y, Pohl NM, Zhou T, Jiménez-Pérez L, Ayon RJ, Desai AA, Goltzman D, Rischard F, Khalpey ZI, Black SM, Garcia JG, Makino A, Yuan JX.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: in press Issue: 9 Pages: L846-L859
  • DOI: 10.1152/ajplung.00050.2016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Calcilytics enhance sildenafil-induced antiproliferation in idiopathic pulmonary arterial hypertension. (2016)
  • Author(s): Yamamura A, Yagi S, Ohara N, Tsukamoto K.
  • Journal Title: Eur J Pharmacol. Volume: 784 Pages: 15-21
  • DOI: 10.1016/j.ejphar.2016.04.059
  • Peer Reviewed
• [Journal Article] 肺循環薬理学研究の最前線：序文 (2016)
  • Author(s): 平野勝也, 山村彩
  • Journal Title: 日薬理誌 Volume: 148(5) Pages: 225-225
  • Open Access
• [Journal Article] Upregulation/downregulation of ion channels in pulmonary hypertension (2016)
  • Author(s): 山村彩
  • Journal Title: Folia Pharmacologica Japonica Volume: 148 Issue: 5 Pages: 226-230
  • DOI: 10.1254/fpj.148.226
  • NAID: 130005268016
  • ISSN: 0015-5691, 1347-8397
  • Open Access
• [Journal Article] Calcium-sensing receptor (2016)
  • Author(s): 山村彩
  • Journal Title: Folia Pharmacologica Japonica Volume: 148 Issue: 5 Pages: 278-280
  • DOI: 10.1254/fpj.148.278
  • NAID: 130005268095
  • ISSN: 0015-5691, 1347-8397
  • Open Access
• [Journal Article] 肺高血圧症におけるカルシウムシグナル (2016)
  • Author(s): 山村彩
  • Journal Title: BIO Clinica Volume: 31(6) Pages: 634-641
• [Journal Article] Notch Activation of Ca2+ Signaling Mediates Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension (2015)
  • Author(s): Smith KA, Voiriot G, Tang H, Fraidenburg DR, Song S, Yamamura H, Yamamura A, Guo Q, Wan J, Pohl NM, Tauseef M, Bodmer R, Ocorr K, Thistlethwaite PA, Haddad GG, Powell FL, Makino A, Mehta D, Yuan JX
  • Journal Title: Am J Respir Cell Mol Biol Volume: in press Issue: 3 Pages: 355-367
  • DOI: 10.1165/rcmb.2014-0235oc
  • Peer Reviewed
• [Journal Article] Peripheral gene expression profile of mechanical hyperalgesia induced by repeated cold stress in SHRSP5/Dmcr rats. (2015)
  • Author(s): Kozaki Y, Umetsu R, Mizukami Y, Yamamura A, Kitamori K, Tsuchikura S, Ikeda K, Yamori Y.
  • Journal Title: J Physiol Sci. Volume: 65(5) Issue: 5 Pages: 417-425
  • DOI: 10.1007/s12576-015-0380-9
  • NAID: 120005952825
  • Peer Reviewed
• [Journal Article] Inhibition of excessive cell proliferation by calcilytics in idiopathic pulmonary arterial hypertension. (2015)
  • Author(s): Yamamura A, Ohara N, Tsukamoto K.
  • Journal Title: PLoS One Volume: 10(9) Issue: 9 Pages: e0138384-e0138384
  • DOI: 10.1371/journal.pone.0138384
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 肺動脈平滑筋におけるCa2+シグナルの異常 (2015)
  • Author(s): 山村彩、山村寿男
  • Journal Title: 東邦医会誌 Volume: 62（3） Pages: 200-202
• [Presentation] 肺高血圧症由来細胞の異常増殖に対するCaSR阻害薬とPDE5阻害薬の併用効果 (2017)
  • Author(s): 山村彩、藤冨恵吏、八木聡美、大原直樹、塚本喜久雄
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
• [Presentation] CaSR阻害薬とPDE5阻害薬の併用は肺高血圧症モデル細胞の異常増殖を相加相乗的に抑制する (2017)
  • Author(s): 山村彩、藤冨恵吏、八木聡美、大原直樹、塚本喜久雄
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
• [Presentation] 肺高血圧症由来細胞の異常増殖に対するCaSR阻害薬とPDE5阻害薬の相加・相乗的抑制効果 (2017)
  • Author(s): 山村彩、藤冨恵吏、八木聡美、大原直樹、塚本喜久雄
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松
• [Presentation] 肺高血圧症由来肺動脈平滑筋細胞におけるカルシウム感受性受容体拮抗薬の抗増殖作用 (2016)
  • Author(s): 山村彩、八木聡美、鈴村紗世、大原直樹、塚本喜久雄
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
• [Presentation] Ca2+感受性受容体阻害薬による肺高血圧症由来肺動脈平滑筋細胞の増殖抑制 (2016)
  • Author(s): 山村彩、八木聡美、鈴村紗世、大原直樹、塚本喜久雄
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-10
• [Presentation] Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) attenuated experimental pulmonary hypertension. (2016)
  • Author(s): Chen J, Sysol JR, Shioura KM, Singla S, Yamamura H, Yamamura A, Reddy V, Torres J, Sridhar A, Tang H, Yuan JX, Garcia JG, Machado RF.
  • Organizer: AFMR Midwestern Regional Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] Pathological roles of calcium-sensing receptors and transient receptor potential canonical channels 6 in the development and progression of pulmonary hypertension. (2016)
  • Author(s): Tang H, Gu Y, Black SM, Garcia JG, Makino A, Yuan JX, Yamamura A, Fraidenburg DR, Chen J.
  • Organizer: AFMR Midwestern Regional Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] 細胞増殖を指標とした肺高血圧症治療薬評価系の開発 (2016)
  • Author(s): 藤冨恵吏、塚本喜久雄、大原直樹、山村彩
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2016
  • Place of Presentation: 仙台
• [Presentation] 肺高血圧症モデルラットで発現増加するカルシウム感受性受容体の性差による影響 (2015)
  • Author(s): 鈴村紗世、堀井千裕、平工 明里、塚本喜久雄、大原直樹、山村彩
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2015
  • Place of Presentation: 東京
  • Year and Date: 2015-08-29
• [Presentation] 低酸素誘発性肺高血圧症モデル動物におけるカルシウム感受性受容体拮抗薬の効果 (2015)
  • Author(s): 山村彩、鈴村紗世、大原直樹、塚本喜久雄
  • Organizer: 第57回日本平滑筋学会総会
  • Place of Presentation: 山口
  • Year and Date: 2015-08-27
• [Presentation] 肺高血圧症を増悪させるジヒドロピリジン系カルシウムチャネルブロッカーの分子機構の解明 (2015)
  • Author(s): 山村彩
  • Organizer: 第61回日本薬学会東海支部総会・大会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-07-04
  • Invited
• [Remarks] 金城学院大学 学術研究データベース
  • URL: http://tdb.kinjo-u.ac.jp/search/index.php/search/teacher_info?teacherid=12847
• [Remarks] 金城学院大学 学術研究データベース
  • URL: http://tdb.kinjo-u.ac.jp/search/