Regulatory mechanisms of endothelial-specific expression and cellular functions of Tmem100 during vascular formation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K21249
• Project/Area Number (Other): 18H06134 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Liu Norika (Mengchia) 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (50826922)
• Project Period (FY): 2018-08-24 – 2021-03-31
• Keywords: 血管内皮細胞 / Tmem100 / 転写制御機構 / 血管リモデリング / 新生仔網膜

Outline of Final Research Achievements

The present study aimed to unveil regulatory mechanisms of Tmem100 expression and cellular functions during vascular formation. The BAC transgenic mouse reporter analysis was performed to search for an endothelial enhancer of Tmem100. We found a group of endothelial transcription factors that activate the endothelial enhancer of Tmem100. Moreover, we have created an EGFP fluorescent reporter mouse line using the BAC constructs described above. On the other hand, to explore the molecular function of Tmem100, the retinal vasculature of neonatal mice with the endothelial-specific inducible gene deletion was analyzed. This phenotypic analysis revealed that Tmem100 had important morphogenic roles in arterial endothelial cells. We are currently addressing the partner proteins that are required for Tmem100 to function in vascular formation.

Free Research Field

血管生物医学

Academic Significance and Societal Importance of the Research Achievements

TMEM100欠損はOsler病や肺動脈性肺高血圧症をはじめとした難治性ヒト血管疾患に重要な役割を持つことが想定されている。よって、本研究にてTmem100の発現制御機構と機能メカニズムを解明することで、上記のような血管形成異常や遺伝性血管病の疾患機序に関与する新たな治療ターゲットとしての有用性を示す可能性を持つ。
また、EGFPレポーターマウス系統を作成したことは、マウス胎生中期の血管形成過程において中・大動脈内皮細胞をFACS精製するツールとして有用であす。これまでに中・大動脈特異的な内皮細胞のレポーターマウスは存在せず、網羅的遺伝子発現・プロテオーム解析などに用いることが期待される。