The importance of polyamine activation in pulmonary hypertension

• Project/Area Number: 15K15318
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: SAKAI Satoshi 筑波大学, 医学医療系, 講師 (30282362)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肺高血圧症 / ポリアミン / メタボローム解析

Outline of Final Research Achievements

It occurs that marked increase of pulmonary arterial smooth muscle cells (PASMCs) in pulmonary arterial hypertension (PAH). By metabolomics analysis, the concentration of polyamine was significantly elevated in the lungs of hypoxia-induced PAH mice. By microarray analysis, the gene expression of S-adenosyl methionine decarboxylase in the lungs was markedly increased in PAH mice. Taken together, the augmentation of polyamine concentration would be due to the increased synthesis of decarboxylated S-adenosyl methionine, which was induced by the enhanced activity of S-adenosyl methionine decarboxylase. Because polyamine contributes to the proliferation of cancer cells, the increase of polyamine production in the lungs would also be involved in the enhanced proliferation of PASMCs in PAH, probably in a similar fashion.

Research Products

• [Journal Article] Antagonists to endothelin receptor type B promone apoptosis in human pulmonary arterial smooth muscle cells. (2016)
  • Author(s): Sakai S, Maruyama H, Kimura T, Tajiri K, Honda J, Homma S, Aonuma K, Miyauchi T
  • Journal Title: Life Sci Volume: In print Pages: 116-120
  • DOI: 10.1016/j.lfs.2016.03.044
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bosentan reverses the hypoxia-induced downregulation of the bone morphogenetic protein signaling in pulmonary artery smooth muscle cells (2016)
  • Author(s): Maruyama, H. Dewachter, C. Sakai, S. Belhaj, A. Rondelet, B. Remmelink, M. Vachiery, J. L. Naeije, R. Dewachter, L.
  • Journal Title: Life Sci Volume: 159 Pages: 111-115
  • DOI: 10.1016/j.lfs.2016.05.018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension (2016)
  • Author(s): Tahara N, Dobashi H, Fukuda K, Funauchi M, Hatano M, Ikeda S, Joho S, Kihara Y, Kimura T, Kondo T, Matsushita M, Minamino T, Nakanishi N, Ozaki Y, Saji T, Sakai S, Tanabe N, Watanabe H, Yamada H, Yoshioka K, Sasayama S
  • Journal Title: Circulation Journal Volume: 80 Issue: 6 Pages: 1478-1483
  • DOI: 10.1253/circj.CJ-15-1305
  • NAID: 130005153579
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] p62 modulates the intrinsic signaling of UVB-induced apoptosis. (2016)
  • Author(s): Ito S, Kimura S, Warabi E, Kawachi Y, Yamatoji M, Uchida F, Ishibashi-Kanno N, Yamagata K, Hasegawa S, Shoda J, Tabuchi K, Sakai S, Bukawa H, Sekido M, Yanagawa T.
  • Journal Title: Journal of Dermatological Science Volume: 83 Issue: 3 Pages: 226-233
  • DOI: 10.1016/j.jdermsci.2016.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis (2016)
  • Author(s): Osamu Baba,Shogo Hasegawa,Hiroki Nagai,Fumihiko Uchida,Masanobu Yamatoji,Naomi I. Kanno,Kenji Yamagata,Satoshi Sakai,Toru Yanagawa,Hiroki Bukawa
  • Journal Title: Journal of Oral Pathology & Medicine Volume: 45 Issue: 4 Pages: 248-255
  • DOI: 10.1111/jop.12351
  • NAID: 120007135548
  • Peer Reviewed / Open Access
• [Journal Article] Endothelin-Bone morphogenetic protein type 2 receptor interaction induces pulmonary artery smooth muscle cell hyperplasia in pulmonary arterial hypertension (2015)
  • Author(s): Maruyama H, Dewachter C, Belhaj A, Rondelet B, Sakai S, Remmeling M, Vachiery J, Naeije R, Dewachter L
  • Journal Title: J Heart Lung Transplantat Volume: 34 Issue: 3 Pages: 468-478
  • DOI: 10.1016/j.healun.2014.09.011
  • Peer Reviewed / Int'l Joint Research
• [Presentation] The decrease of S-wave amplitude in V5 lead of electrocardiography positively reflects effectual treatment in patients with pulmonary hypertension (2017)
  • Author(s): Otsu K, Sakai S, Kimura T, Miyauchi T, Homma S, Aonuma K
  • Organizer: 第８１回日本循環器学会学術集会
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2017-03-17
• [Presentation] ヒト肺動脈血管平滑筋細胞に対するETB受容体遮断による影響 (2016)
  • Author(s): 酒井俊・丸山秀和・木村泰三・田尻和子・本田洵也・本間覚・青沼和隆・宮内卓
  • Organizer: 第20回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京コンベンションホール（東京都中央区）
  • Year and Date: 2016-12-16
• [Presentation] Hypoxia induces the down regulation of the BMP signaling in pulmonary artery smooth muscle cells through the endothelin system (2016)
  • Author(s): Maruyama H, Sakai S, Naeije R, Dewachter L, Aonuma K
  • Organizer: Congress of the European-Society-of-Cardiology (ESC) 2016
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Lysol oxidase was increased by endothelin-1 and restored by PGI2 in pulmonary artery smooth muscle cells (2016)
  • Author(s): Maruyama H, Sakai S, Naeije R, Dewachter L, Aonuma K
  • Organizer: Congress of the European-Society-of-Cardiology (ESC) 2016
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Pulmonary hypertension is ameliorated by glucagon-like peptide-1 receptor agonist partly via eNOS activation (2016)
  • Author(s): Sakai S, Kimura T, Honda J, Tajiri K, Homma S, Aonuma K, Miyauchi T
  • Organizer: The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications f Nitric Oxide
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-05-20
  • Int'l Joint Research
• [Presentation] 肺高血圧進展におけるPin1 (Peptidyl isomerase1) の役割 (2015)
  • Author(s): 酒井 俊
  • Organizer: 第4回日本肺循環学会・第3回日本肺高血圧学会合同学術集会
  • Place of Presentation: 東京 東京ステーションコンファレンス
  • Year and Date: 2015-10-03
• [Presentation] Effects of endothelin receptor antagonists on doxorubicin-induced apoptosis in vascular smooth muscle cells derived from human pulmonary artery (2015)
  • Author(s): Sakai S, et al.
  • Organizer: 14th International Conference on Endothelin
  • Place of Presentation: Savannah, GA, USA
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] Bosentan reverses the hypoxia-induced downregulation of the bone morphogenetic protein signaling in pulmonary artery smooth muscle cells (2015)
  • Author(s): Maruyama H, Sakai S, et al
  • Organizer: 14th International Conference on Endothelin
  • Place of Presentation: Savannah, GA, USA
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] The glucagon-like peptide-1 receptor agonist improves hypoxia induced pulmonary hypertension in mice model (2015)
  • Author(s): Kimura T, Sakai S, et al.
  • Organizer: Congress of the European-Society-of-Cardiology (ESC)
  • Place of Presentation: London, UK
  • Year and Date: 2015-08-29
  • Int'l Joint Research