Development of Ductus Arteriosus Regulation Targeting Adenylyl Cyclases without Side Effect

• Project/Area Number: 21591418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Yokohama City University
• Principal Investigator: IWASAKI Shiho 横浜市立大学, 医学部, 准教授 (10347338)
• Co-Investigator(Renkei-kenkyūsha): YOKOYAMA Utako 横浜市立大学, 医学部, 講師 (70404994)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 動脈管 / アデニル酸シクラーゼ

Research Abstract

Prostaglandin E induces vasodilation and intimal thickening(IT) in the ductus arteriosus via activation of adenylyl cyclases(AC). We revealed that AC6 is responsible for hyaluronan production and AC2 inhibited it. Stimulation of both AC2 and AC6 by FD1 induced longer vasodilation without IT. FD1 may be a novel alternative therapy to currently available PGE therapy for ductus arteriosus.

Research Products

• [Journal Article] Immune responseto Haemophilus influenzae type b conjugate vaccine in preterm infants (2012)
  • Author(s): Tsuda K, Iwasaki S, Horiguchi H, Mori M, Nishimaki S, Seki K, Taguri M, Yokota S, Ishiwada N
  • Journal Title: Pediatr Int Volume: 54(1) Pages: 64-7
  • Peer Reviewed
• [Journal Article] Urinaryβ2-microglobulin in very preterm neonates with chorioamnionitis (2011)
  • Author(s): Nishimaki S, Shima Y, Sato M, An H, Fujita S, Iwasaki S, Horiguchi H, Seki K, Yokota S
  • Journal Title: Pediatri Nephrol Volume: 26(12) Pages: 2185-91
  • Peer Reviewed
• [Journal Article] Early discharge from a neonatal intensive care unit and rates of readmission (2011)
  • Author(s): Seki K, Iwasaki S, An H, Horiguchi H, Mori M, Nishimaki S, Yokota S
  • Journal Title: Pediatr Int Volume: 53(1) Issue: 1 Pages: 7-12
  • DOI: 10.1111/j.1442-200x.2010.03179.x
  • NAID: 10029556906
  • Peer Reviewed
• [Journal Article] Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus (2010)
  • Author(s): Yokoyama U, Minamisawa S, Katayama A, Tang T, Suzuki S, Iwatsubo K, Iwasaki S, Kurotani R, Okumura S, Sato M, Yokota S, Hammond HK, Ishikawa Y
  • Journal Title: Circ Res Volume: 106(12) Issue: 12 Pages: 1882-1892
  • DOI: 10.1161/circresaha.109.214924
  • Peer Reviewed
• [Journal Article] Regulation of vascular tone and remodeling of the ductus arteriosus (2010)
  • Author(s): Yokoyama U, Minamisawa S, Ishikawa Y
  • Journal Title: J. Smooth Muscle Res Volume: 46(2) Pages: 77-87
  • NAID: 10030687229
  • Peer Reviewed
• [Journal Article] Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus (2010)
  • Author(s): 岩崎志穂
  • Journal Title: Circ Res. Volume: 25 Pages: 1882-1892
  • Peer Reviewed
• [Journal Article] Soluble tumor necrosis factor receptor-I in preterm infants with chorioamnionitis (2009)
  • Author(s): Sato M, Nishimaki S, An H, Shima Y, Naruto T, Sugai T, Iwasaki S, Seki K, Imagawa T, Mori M, Yokota S
  • Journal Title: J Obstet Gynaecol Res Volume: 35(2) Pages: 252-7
  • NAID: 10025339217
  • Peer Reviewed
• [Journal Article] たとえで簡単新生児呼吸器疾患とそのケア、呼吸急迫症候群 (2009)
  • Author(s): 岩崎志穂
  • Journal Title: Neonatal care Volume: 22 Pages: 1238-1243
• [Journal Article] T-type Ca2+channels promote oxygenation-induced closure of the rat ductus arteriosus not only by vasoconstriction but also by neointima formation (2009)
  • Author(s): Akaike T, Jin MH, Yokoyama U, Izumi-Nakaseko H, Jiao Q, Iwasaki S, Iwamoto M, Nishimaki S, Sato M, Yokota S, Kamiya Y, Adachi-Akahane S, Ishikawa Y, Minamisawa S
  • Journal Title: J Biol Chem Volume: 284(36) Issue: 36 Pages: 24025-24034
  • DOI: 10.1074/jbc.m109.017061
  • Peer Reviewed
• [Journal Article] 【たとえでかんたん 新生児呼吸器疾患とそのケア】呼吸窮迫症候群 (2009)
  • Author(s): 岩崎志穂
  • Journal Title: Neonatal Care 22巻 Pages: 1238-1243
• [Presentation] Oxygenation-induced postnatal remodeling of the ductus arteriosus (2012)
  • Author(s): Jin MH, Yokoyama U, Ishiwata R, Minamisawa S, IshikawaY
  • Organizer: The 89^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 松本文化体育館,長野
  • Year and Date: 2012-03-30
• [Presentation] Inhibition of Phophodiesterase Type 3 Milrinone Dilate the Ductus Arteriosus without Forming Intimal Thickening (2012)
  • Author(s): Ichikawa Y, Yokoyama U, Ishikawa Y
  • Organizer: The 89^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 松本文化体育館,長野
  • Year and Date: 2012-03-30
• [Presentation] Inhibition of EP4 Signaling Attenuates Mouse Aortic Aneurysm Formation (2012)
  • Author(s): Yokoyama U, Jin MH, Kato Y, Ishiwata R, Suzuki S, Masuda M, Asou T, Aoki H, Sugimoto Y, Nakamura T, Minamisawa S, Ishikawa Y
  • Organizer: The 76^<rd> Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 福岡国際会議場,福岡
  • Year and Date: 2012-03-17
• [Presentation] 動脈管収縮における出生後の血清浸透圧低下の役割 (2011)
  • Author(s): 青木理加, 横山詩子, 岩崎志穂, 関和男, 西巻滋, 横田俊平, 石川義弘
  • Organizer: 第56回日本未熟児新生児学会学術集会
  • Place of Presentation: 東京国際フォーラム,東京
  • Year and Date: 2011-11-14
• [Presentation] Regulation of vascular remodeling of the ductus arteriosus (2011)
  • Author(s): Yokoyama U, Minamisawa S, Ishikawa Y
  • Organizer: The 88th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: パシフィコ横浜,神奈川
  • Year and Date: 2011-03-29
• [Presentation] Prostaglandin EP4 Signaling Negatively Regulates Vascular Elastic Fiber Assembly (2010)
  • Author(s): Yokoyama U, Shioda A, Kato Y, Asou T, Aoki H, Nakamura T, Minamisawa S, Ishikawa Y
  • Organizer: The 84th Scientific Session, American Heart Association(AHA)
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-16
• [Presentation] ラット動脈管閉鎖における低浸透圧センサーTransient Receptor Potential Melastatin3(TRPM3)チャネルの役割 (2010)
  • Author(s): 青木理加, 横山詩子, 岩崎志穂, 西巻滋, 横田俊平, 石川義弘
  • Organizer: 第55回未熟児新生児学会・学術集会
  • Place of Presentation: 神戸国際会議場,兵庫
  • Year and Date: 2010-11-07
• [Presentation] ラット動脈管内膜肥厚におけるアデニル酸シクラーゼアイソフォームの役割の検討 (2010)
  • Author(s): 岩崎志穂
  • Organizer: 第46回日本周産期・新生児医学会
  • Place of Presentation: 神戸・神戸国際会議場
  • Year and Date: 2010-07-13
• [Presentation] Prostaglandin E2-activated Epac promotes neointimal formation of the rat ductus arteriosus by a process distinct from that of cAMP-dependent protein kinase A (2010)
  • Author(s): 横山詩子
  • Organizer: 第52回日本平滑筋学会総会栗山煕賞受賞記念講演
  • Place of Presentation: 仙台市情報プラザアエル,宮城
  • Year and Date: 2010-07-01
• [Presentation] ラット動脈管内膜肥厚におけるアデニル酸シクラーゼアイソフォームの役割の検討 (2010)
  • Author(s): 岩崎志穂, 青木理加, 西巻滋, 横田俊平, 南沢享, 横山詩子
  • Organizer: 第46回日本周産新生児医学会
  • Place of Presentation: 神戸国際会議場,兵庫
• [Presentation] A Role of Thromboxane A2 Receptor in the Rat Ductus Arteriosus as a Vasoconstrictor (2010)
  • Author(s): Yokota T, Ozawa M, Yokoyama U, Minamisawa S
  • Organizer: The 16th International Vascular Biology Meeting
  • Place of Presentation: Los Angeles, USA
• [Presentation] Counteracting regulation of vascular remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus (2010)
  • Author(s): Minamisawa S, Yokoyama U, Akaike T, Hammond K, Ishikawa Y
  • Organizer: The 16^<th> International Vascular Biology Meeting
  • Place of Presentation: Los Angeles, USA
• [Presentation] Oxygenation Promotes Migration of Smooth Muscle Cell in the Rat Ductus Arteriosus (2010)
  • Author(s): Minamisawa S, Akaike T, Yokoyama U, Iwasaki S, Ishikawa Y
  • Organizer: Developmental Vascular Biology Workshop IV
  • Place of Presentation: Monterey, California
• [Presentation] Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus (2010)
  • Author(s): Yokoyama U, Minamisawa S, Katayama A, Tang T, Iwasaki S, Hammond HK, Ishikawa Y
  • Organizer: Developmental Vascular Biology Workshop IV
  • Place of Presentation: Monterey, California
• [Presentation] プロスタグランジンの予期せぬ役割Molecular Mechanisms of Closure of Dactus Arteriosus : Unexpected roles of prostaglandins (2009)
  • Author(s): 南沢享, 横山詩子
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、神奈川
• [Presentation] 胎生後期ラット動脈管におけるTRPMチャネルの発現～大動脈組織との比較検討～ (2009)
  • Author(s): 青木理加, 横山詩子, 岩崎志穂, 西巻滋, 横田俊平, 石川義弘
  • Organizer: 第54回日本未熟児新生児学会・学術集会
  • Place of Presentation: パシフィコ横浜,神奈川
• [Presentation] プロスタグランディンE受容体EP4シグナルによる弾性線維形成の制御 (2009)
  • Author(s): 横山詩子, 南沢享, 片山綾子, 塩田亜樹, 中邨智之, 杉本幸彦, 石川義弘
  • Organizer: 第13回Molecular Cardiovascular Conference
  • Place of Presentation: 北海道
• [Presentation] Oxygenation Promotes Smooth Muscle Cell Migration in the Rat Ductus Arteriosus (2009)
  • Author(s): Minamisawa S, Akaike T, Yokoyama U, Ozawa M, Iwasaki S, Ishikawa I
  • Organizer: BCVS Conference-Molecular Mechanisms of Cardiovascular Diseases
  • Place of Presentation: Lake Las Vegas, Nevada