C/EBPb regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation in female rats

• Project/Area Number: 18K16772
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Yamaguchi University
• Principal Investigator: SHINAGAWA Masahiro 山口大学, 医学部附属病院, 助教 (50814472)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 卵巣顆粒膜細胞 / 血管新生 / VEGF / C/EBPβ / Epigenetics / 黄体化 / C/EBPb / 転写 / 顆粒膜細胞 / 転写調節

Outline of Final Research Achievements

Ovulation and associated luteinization are essential for the establishment and maintenance of pregnancy. Angiogenesis is required for the corpus luteum formation, and the factors that regulate angiogenesis are Vascular Endothelial Growth Factor (Vegf).
We found that C/EBPβ, but not HIF1α, regulates Vegf gene expression by binding to the novel binding site in the rat Vegf promoter region. In addition to transcription factors, histone modifications and chromatin structure of the Vegf promoter region are involved in the regulation of Vegf expression.

Academic Significance and Societal Importance of the Research Achievements

本研究により、我々はラット顆粒膜細胞におけるVegf遺伝子発現制御にC/EBPbが関与していることを初めて示した。Vegf は血管新生に重要な役割を担う遺伝子であるため、我々の結果は黄体化過程にある顆粒膜細胞における血管新生の制御機構を理解する一助となると考えられる。

Research Products

• [Journal Article] C/EBPβ regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation in female rats (2019)
  • Author(s): Shinagawa Masahiro、Tamura Isao、Maekawa Ryo、Sato Shun、Shirafuta Yuichiro、Mihara Yumiko、Okada - Matsumoto Maki、Taketani Toshiaki、Asada Hiromi、Tamura Hiroshi、Sugino Norihiro
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41598-018-36566-y
  • Peer Reviewed / Open Access
• [Presentation] ラット顆粒膜細胞の黄体化に伴うVegf遺伝子発現の転写調節機構の解明 (2018)
  • Author(s): 品川征大、田村功、前川亮、白蓋雄一郎、竹谷俊明、浅田裕美、田村博史、杉野法広
  • Organizer: 第91回日本内分泌学会学術総会
• [Presentation] C/EBPβ, but not Hif1α, regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation after the LH surge in female rats (2018)
  • Author(s): M.Shinagawa,I.Tamura,R.Maekawa,Y.Shirafuta,M.Okada,T.Taketani,H.Asada,H.Tamura,N.Sugino
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] ラット顆粒膜細胞の黄体化に伴うVegf遺伝子発現はHIF1aではなくC/EBPbが調節している (2018)
  • Author(s): 品川征大、田村功、前川亮、高木遥香、白蓋雄一郎、三原由実子、佐藤俊、竹谷俊明、 田村博史、杉野法広
  • Organizer: 第23回日本生殖内分泌学会学術総会