Regulatory mechanism of angiogenesis mediated by calcium signaling

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06867
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Wakayama Medical University (2019-2021); National Cardiovascular Center Research Institute (2018)
• Principal Investigator: Nishitani Tomoe 和歌山県立医科大学, 医学部, 教授 (50393244)
• Co-Investigator(Kenkyū-buntansha): 中川 修 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (40283593)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 血管形成 / カルシウムシグナル / Tmem100 / TRP チャネル

Outline of Final Research Achievements

Angiogenesis is an essential process for organogenesis and wound healing. Recently, the importance of intracellular Ca2+ signaling in the process of angiogenesis has been suggested. We have identified Tmem100 as a essential factor for cardiovascular angiogenesis and found that intracellular Ca2+ signaling is involved in its function. In the present study, we investigated the relationship between Tmem100 and various intracellular Ca2+ signal regulators. We found that TRPV4 channels, which play an important role in endothelial functions, physically interact with Tmem100 and co-localize with it in vascular endothelial cells, whereas TRPC6 channels, which are important for vascular smooth muscle, do not bind

Free Research Field

循環器系の細胞生理

Academic Significance and Societal Importance of the Research Achievements

心血管形成機構に関しては、これまで転写因子活性化シグナルの解明に焦点が絞られてきたが、細胞内Ca2+シグナルの重要性を示す研究は未だ新規である。今回、Tmem100とメカノセンサーとして働くTRPチャネルとの機能連関および心血管形成における寄与を証明できれば、①Tmem100のイオンチャネル分子内制御因子としての新規分子機能、②TRPチャネルの心血管形成における重要性、③他の関連因子も含めたCa2+シグナルを介した心血管形成機構の重要性が明らかになり、薬物開発の新たなターゲット探索になる。総じて、ヒト疾患の病因解明・治療法の開発に向けた基礎研究として現代社会に大いに役立つことが期待できる。