The effectiveness of erythropoietin for the pulmonary hypertension with the congenital diaphragmatic hernia patients

• Project/Area Number: 25462769
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: University of Tsukuba
• Principal Investigator: Takayasu Hajime 筑波大学, 医学医療系, 講師 (10359614)
• Co-Investigator(Kenkyū-buntansha): MASUMOTO Kouji 筑波大学, 医学医療系, 教授 (20343329) ; UESUGI Toru 筑波大学, 医学医療系, 講師 (30380421) ; GOTOH Chikashi 筑波大学, 医学医療系, 講師 (80598889)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 先天性横隔膜ヘルニア / ラットモデル / 肺高血圧 / RhoA / エリスロポエチン / ナイトロフェン / Rhoキナーゼ / 横隔膜ヘルニア / Rho Kinase阻害剤 / Wntシグナル伝達系

Outline of Final Research Achievements

Our results using nitrofen-induced congenital diaphragmatic hernia (CDH) provide evidence that the RhoA/Rho-kinase-mediated pathway is involved in the pathogenesis of PH in the nitrofen-induced CDH rat model. Our data also suggest that the fasudil, a Rho-kinase inhibitor, could represent a therapeutic option for the treatment of PH in CDH. We also found the suppressed EPO synthesis in the CDH fetus, which may contribute to the pathogenesis of lung hypoplasia and modification of pulmonary vasculature in the CDH rat model.

Research Products

• [Journal Article] Growth Assessment and the Risk of Growth Retardation in Congenital Diaphragmatic Hernia: A Long-Term Follow-Up Study from the Japanese Congenital Diaphragmatic Hernia Study Grou (2016)
  • Author(s): Terui K, Nagata K, Hayakawa M, Okuyama H, Goishi K, Yokoi A, Tazuke Y, Takayasu H, Yoshida H, Usui N.
  • Journal Title: Eur J Pediatric Surg. Volume: 26 Issue: 01 Pages: 60-6
  • DOI: 10.1055/s-0035-1566094
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Japanese Congenital Diaphragmatic Hernia Study Group. Musculoskeletal abnormalities in congenital diaphragmatic hernia survivors: Patterns and risk factors: report of a Japanese multicenter follow-up survey. (2016)
  • Author(s): Takayasu H, Masumoto K, Goishi K, Hayakawa M, Tazuke Y, Yokoi A, Terui K, Okuyama H, Usui N, Nagata K, Taguchi T
  • Journal Title: Pediatr Int. Volume: 未定 Issue: 9 Pages: 877-880
  • DOI: 10.1111/ped.12922
  • Peer Reviewed
• [Journal Article] Increased pulmonary RhoA expression in the nitrofen-induced congenital diaphragmatic hernia rat model. (2015)
  • Author(s): Takayasu H, Masumoto K, Hagiwara K, Sasaki T, Ono K, Jimbo T, Uesugi T, Gotoh C, Urita Y, Shinkai T, Tanaka H.
  • Journal Title: J Pediatr Surg. Volume: 50 Issue: 9 Pages: 1467-71
  • DOI: 10.1016/j.jpedsurg.2015.02.063
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Analysis of risk factors of long-term complications in congenital diaphragmatic hernia: A single institution's experience. (2015)
  • Author(s): Takayasu H, Masumoto K, Jimbo T, Sakamoto N, Sasaki T, Uesugi T, Gotoh C, Urita Y, Shinkai T.
  • Journal Title: Asian J Surg. Volume: in Press Issue: 1 Pages: 1-5
  • DOI: 10.1016/j.asjsur.2015.02.005
  • NAID: 120007134917
  • Peer Reviewed
• [Presentation] 先天性横隔膜ヘルニアラットモデル腎臓におけるエリスロポエチン産生の抑制 (2016)
  • Author(s): 高安 肇 増本幸二 萩原幸輝 南 洋輔 後藤悠大 千葉史子 坂元直哉 五藤 周 瓜田泰久 新開統子 田中秀明
  • Organizer: 第53回日本小児外科学会
  • Place of Presentation: 博多、ヒルトン福岡シーホーク
  • Year and Date: 2016-05-24
• [Presentation] Growth Assessments and The Risk of Growth Retardation In Congenital Diaphragmatic Hernia: The Multicenter Follow-Up Study (2015)
  • Author(s): Keita Terui , Tomoaki Taguchi, Masahiro Hayakawa, Hiroomi Okuyama, Keiji Goishi, Akiko Yokoi, Yuko Tazuke, Hajime Takayasu, Hideo Yoshida, Noriaki Usui and The Japanese Congenital Diaphragmatic Hernia Study Group
  • Organizer: 第16回ヨーロッパ小児外科学会
  • Place of Presentation: リャブナ、スロベニア
  • Year and Date: 2015-06-17
  • Int'l Joint Research
• [Presentation] Musculoskeletal Abnormalities in Congenital Diaphragmatic Hernia Survivors: Patterns and Risk Factors - Report From A Multicenter Follow-up Survey - (2015)
  • Author(s): Hajime Takayasu, Kouji Masumoto, Keiji Goishi, Masahiro Hayakawa, Yuko Tazuke, Akiko Yokoi, Keita Terui, Hiroomi Okuyama, Noriaki Usui, Kouji Nagata, and Tomoaki Taguchi
  • Organizer: 第52回日本小児外科学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-05-27
• [Presentation] Suppressed Erythropyetin Expression in the Liver in Nitrofen-induced Congenital Diaphragmatic Hernia. (2015)
  • Author(s): Hajime Takayasu, Kouji Masumoto, Koki Hagiwara, Takato Sasaki, Fumiko Chiba, Naoya Sakamoto, Chikashi Gotoh, Yasuhisa Urita, Makoto Nakao, Toko Shinkai, Hideaki Tanaka
  • Organizer: アジア太平洋小児外科学会2015
  • Place of Presentation: チェジュ島、韓国
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Presentation] Suppressed Erythropyetin Expression in the Liver in Nitrofen-induced Congenital Diaphragmatic Hernia. (2015)
  • Author(s): Hajime Takayasu, Kouji Masumoto, Koki Hagiwara, Shunsuke Fujii, Tsubasa Aiyoshi, Takato Sasaki, Fumiko Chiba, Naoya Sakamoto, Chikashi Gotoh, Yasuhisa Urita, Makoto Nakao, Toko Shinkai, Hideaki Tanaka
  • Organizer: 太平洋小児外科学会
  • Place of Presentation: チェジュ島、韓国
  • Year and Date: 2015-05-17 – 2015-05-21
• [Presentation] Increased pulmonary RhoA expression in the nitrofen-induced congenital diaphragmatic hernia (2014)
  • Author(s): Hajime Takayasu, Kouji Masumoto, Kouki Hagiwara, Takahiro Jimbo, Takato Sasaki, Kentaro Ono, Toru Uesugi, Chikashi Gotoh, Yasuhisa Urita, Toko Shinkai Hideaki Tanaka
  • Organizer: ヨーロッパ小児外科学会2014
  • Place of Presentation: アイルランド、ダブリン
  • Year and Date: 2014-06-18 – 2014-06-21
• [Presentation] INCREASED PUMONARY RHOA EXPRESSION IN THE NITROFEN-INDUCED CONGENITAL DIAPHRAGMATIC HERNIA. (2014)
  • Author(s): Hajime Takayasu ,Kouji Masumoto Kouki Hagiwara Takahiro Jimbo Takato Sasaki Kentaro Ono Toru Uesugi Chikashi Gotoh Yasuhisa Urita Toko Shinkai Hideaki Tanaka
  • Organizer: ヨーロッパ小児外科学会
  • Place of Presentation: ダブリン、アイルランド
• [Presentation] NitrofenラットモデルにおけるWnt4遺伝子発現の検討 (2014)
  • Author(s): 高安 肇、増本幸二、新開統子、田中秀明、瓜田泰久、五藤 周、上杉 達、神保教広、小野健太郎、佐々木理人
  • Organizer: 第51回日本小児外科学会学術集会
  • Place of Presentation: 大阪