Overexpression of Daam-1 on pulmonary arterial wall for the pathogenesis of human idiopathic pulmonary arterial hypertension

• Project/Area Number: 26460460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Toho University
• Principal Investigator: WAKAYAMA Megumi 東邦大学, 医学部, 講師 (40230924)
• Co-Investigator(Kenkyū-buntansha): 渋谷 和俊 東邦大学, 医学部, 教授 (20196447)
• Research Collaborator: YANAI Shun ; SHIMODAIRA Kayoko ; SHINOZAKI Minoru
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 特発性肺動脈性肺高血圧症 / Wnt/PCPパスウェイ / Daam-1 / Dvl-2 / 肺動脈中膜平滑筋細胞 / IPAH / WNT/PCPパスウェイ / 免疫組織染色 / Stachybotrys chartarum

Outline of Final Research Achievements

Evidence from our recent study suggests that idiopathic pulmonary arterial hypertension (IPAH) pathogenesis is related to upregulation of the Wnt/PCP pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins - namely Wnt-11, Dvl-2, and Daam-1 - in pulmonary arteries.
We analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained 9 IPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary arterial abnormalities, and marked expression of Dvl-2 and Daam-1 was confirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in contrast with specimens from associated pulmonary arterial hypertension cases and controls. So it was suggested that high Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH.

Research Products

• [Journal Article] Implication of overexpression of deshevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH) (2017)
  • Author(s): Yanai S, Wakayama M, Nakayama H, Shinozaki M, Tsukuma H, Tochigi N, Nemoto T, Saji T, Shibuya K
  • Journal Title: DIAGNOSTIC PATHOLOGY Volume: 12 Issue: 1 Pages: 25-35
  • DOI: 10.1186/s13000-017-0614-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Technical Aspects and Applications for Developing <I>in situ</I> Hybridization Procedures for Formalin-Fixed and Paraffin-Embedded (FFPE) Tissues for Diagnosis of Fungal Infections (2017)
  • Author(s): Minoru Shinozaki, Naobumi Tochigi, Sota Sadamoto, Somay Yamagata Murayama, Megumi Wakayama, Tetsuo Nemoto, Kazutoshi Shibuya
  • Journal Title: Medical Mycology Journal Volume: 58 Issue: 1 Pages: E33-E37
  • DOI: 10.3314/mmj.16-00025
  • NAID: 130005401917
  • ISSN: 2185-6486, 2186-165X
• [Journal Article] Genomic analysis for single nucleotide polymorphisms (Asp299Gly and Thr399lle) in Japanese patients with invasive aspergillosis (2015)
  • Author(s): Aki K, Okubo Y, Nanjo H, Ishiwatari T, Nihonyanagi Y, Tochigi N, Wakayama M, Nemoto T, Fukutake K, Shinozaki M, Hori Y, Masuda H, Shibuya K
  • Journal Title: Jpn J Infect Dis Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison between the location and the histomorphological/immunohistochemical characteristics of noninvasive neoplasms of the ampulla of Vater (2014)
  • Author(s): Yamamoto Y, Nemoto T, Okubo Y, Nihonyanagi Y, Ishiwatari T, Takuma K, Tochigi N, Okano N, Wakayama M, Igarashi Y, Shibuya K
  • Journal Title: Hum Pathol Volume: 45 Issue: 9 Pages: 1910-7
  • DOI: 10.1016/j.humpath.2014.05.013
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Pathological study of WNT/PCP signaling system inducing pulmonary arterial remodeling in mice by tntratracheal injection of Stachybotrys chartarum. (2015)
  • Author(s): Megumi Wakayama, Kayoko Shimondaira, Eri Ochiai, Yoichiro Okubo, Minoru Shinozaki, Kyoko Aki, Kozue Ejima, Takao Ishiawatari, Yasuhiro Nihonyanagi, Naobumi Tochigi, Aki Mitsuda, Tetsuo Nemoto, Somay Yamagata Murayama, Katsuhiko Kamei, Kazutoshi Shibuya
  • Organizer: 19th congress of the international society for human and animal mycology
  • Place of Presentation: Melbourne Convention & Exhibition Centre, Melbourne, Australia
  • Year and Date: 2015-05-06
  • Int'l Joint Research
• [Presentation] 肺動脈性肺高血圧症におけるWNT/PCP Pathway関連遺伝子の発現に関する免疫組織学的検討 (2015)
  • Author(s): 若山 恵、下平佳代子、大久保陽一郎、石渡誉郎、二本柳康博、栃木直文、密田亜希、根本哲生、渋谷和俊
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-05-01
• [Presentation] Wnt/PCP Pathway関連因子の特発性肺動脈性肺高血圧症の肺動脈病変における発現 (2014)
  • Author(s): 下平 佳代子, 高月 晋一, 中山 智孝, 若山 恵, 松裏 裕行, 渋谷 和俊, 佐地 勉
  • Organizer: 第50回日本小児循環器学会総会・学術集会
  • Place of Presentation: 岡山コンベンションセンター（岡山県岡山市）
  • Year and Date: 2014-07-04