Analysis of the molecular and cellular mechanism of vessel maturation in adult tissues

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07116
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Shinshu University
• Principal Investigator: Numaga-Tomita Takuro (沼賀拓郎) 信州大学, 学術研究院医学系, 准教授 (60705060)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 血管成熟 / 血管平滑筋 / TRPC6チャネル

Outline of Final Research Achievements

The functional blood vessels play critical roles in body homeostasis. While blood vessels were developmentally formed, once adult tissue have injured, newly formed vascular network contributes to recovery of tissue homeostasis. Formation of functional vascular network requires vessel maturation in which vulnerable nascent capillaries are covered and stabilized by mural cells. Since vessel maturation was complex process involving many factors, the comprehensive molecular and cellular mechanism is still unknown. In this study, we demonstrated that TRPC6 expressed in vascular smooth muscle cells functions as a negative regulator of vessel maturation and the pharmacological suppression of TRPC6 facilitates it even with the endothelial dysfunction. Therefore, TRPC6 could be a druggable target for the ischemic diseases.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、血管平滑筋に発現するTRPC6チャネルが成体における血管成熟の負の制御因子であることを明らかにした。TRPC6を抑制した血管平滑筋細胞およびマウス個体の解析から、TRPC6の抑制が、どのような分子・細胞機構により血管成熟を促進させうるかが明らかになった。本研究における特に重要な発見が、TRPC6の抑制により、血管平滑筋の分化を促進すると内皮障害のレベルも軽減されることである。すなわち、血管平滑筋の表現型の正常化こそが血管の恒常性維持に重要であることが示された。TRPC6は明らかにそこに関与する重要な分子の一つであり、虚血性疾患の予後改善などに有効な創薬標的であることを明らかにした。