To determine the relation between Yap transcriptional activity and the rate of atherosclerosis progression

• Project/Area Number: 16K19391
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: Terai Kenta 京都大学, 生命科学研究科, 准教授 (20616073)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Hippo pathway / 膜性骨化 / fluid shear stress / 血管新生 / 骨分化 / 動脈硬化 / ゼブラフィッシュ / 血管内皮 / イメージング / 循環器・高血圧

Outline of Final Research Achievements

The role of blood vessels during endochondral ossification is well known, while their role in intramembranous ossification, especially the intertissue pathway, is poorly understood. Here, we demonstrate endothelial Yap/Taz is a novel regulator of intramembranous ossification in zebrafish. Appropriate blood flow is required for Yap/Taz transcriptional activation in endothelial cells and intramembranous ossification. Additionally, Yap/Taz transcriptional activity in endothelial cells specifically promotes intramembranous ossification. BMP expression by Yap/Taz transactivation in endothelial cells is also identified as a bridging factor between blood vessels and intramembranous ossification. Furthermore, the expression of Runx2 in pre-osteoblast cells is a downstream target of Yap/Taz transcriptional activity in endothelial cells. Our results provide novel insight into the relationship between blood flow and ossification by demonstrating intertissue regulation.

Research Products

• [Journal Article] Yap/Taz transcriptional activity is essential for vascular regression via Ctgf expression and actin polymerization. (2017)
  • Author(s): Nagasawa-Masuda A, Terai K.
  • Journal Title: PLoS One. Volume: 12(4) Issue: 4 Pages: e0174633-e0174633
  • DOI: 10.1371/journal.pone.0174633
  • Peer Reviewed / Open Access
• [Journal Article] Flow-dependent endothelial YAP regulation that contributes to vessel maintenance. (2017)
  • Author(s): Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H, Fukuhara S, Ando K, Miyazali T, Yokota Y, Sxhmelzer E, Belting H, Affolter M, Lecaudey, Mochizuki N
  • Journal Title: Developmental Cell Volume: 40 Issue: 6 Pages: 523-536
  • DOI: 10.1016/j.devcel.2017.02.019
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Osteocrin, a secretory peptide from heart, contributes to cranial osteogenesis in zebrafish (2016)
  • Author(s): Chiba A, Watanabe-Takano H, Terai K, Fukui H, Miyazaki T, Uemura M, Hashimoto H, Hibi M, Fukuhara S, Mochizuki N
  • Journal Title: Development Volume: 144 Pages: 334-344
  • DOI: 10.1242/dev.143354
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Yap/Taz transcriptional activity in endothelial cells promotes intramembranous ossification via the BMP pathway. (2016)
  • Author(s): Uemura M, Nagasawa A, Terai K.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 27473-27473
  • DOI: 10.1038/srep27473
  • Peer Reviewed / Open Access