Identification of extracellular matrix molecules that regulate fenestra formation in capillaries and their regulatory mechanisms.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07257
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Teikyo University
• Principal Investigator: Nakakura Takashi 帝京大学, 医学部, 講師 (60568658)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 有窓型毛細血管 / 窓 / 基底膜 / 下垂体 / 細胞外マトリックス

Outline of Final Research Achievements

Fenestrated capillaries are distributed in various organs, such as the endocrine glands and small intestine. Fenestrae are about 70 nm in diameter and are organized as clusters of pores called sieve plates. Each fenestral pore is divided by a diaphragm consisting of plasmalemma vesicle-associated protein (PLVAP), a molecular component of fenestral diaphragm. They function as channels for blood and tissue trafficking of peptide hormones and other substances.
In this project, we first established a novel culture method for fenestrated endothelial cells in the anterior pituitary of rats. We also demonstrated that fibronectin-integrin α5β1 signaling regulates the formation of microtubule cytoskeletons to control the transport of PLVAP at the endothelial fenestrae. We then found that the interaction between the actin cytoskeleton and dynamin2 is essential for endothelial fenestra formation in the rat pituitary.

Free Research Field

内分泌形態学

Academic Significance and Societal Importance of the Research Achievements

有窓型毛細血管は下垂体や小腸といった正常組織のほか、がん組織にも分布することが知られる。本課題の遂行で得た研究成果は、毛細血管の有窓性調節における細胞外マトリックスやエンドサイトーシス調節分子との関係性および重要性を示す新知見であるとともに、今後これらの分子に着目した研究をさらに発展させることで、有窓性調節の分子機序の全貌解明のみならず、新しいがん治療戦略への応用も展望できる可能性を秘めている。