Development of a mouse model analysis system to understand the breakdown of tissue function due to microvascular network abnormalities

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20744
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: University of Miyazaki
• Principal Investigator: Ogoh Honami 宮崎大学, 医学部, 助教 (30813290)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 毛細血管 / ぺリサイト / 老化 / 加齢 / 生活習慣病 / 皮膚 / マウス / Col4

Outline of Final Research Achievements

Using lifestyle-related disease-induced mice, we investigated changes in vascular density and the effects of vascular endothelial cell-pericyte interactions on tissues using fluorescent immunostaining, EVG staining, and vascular microscopy. In lifestyle-related disease-induced mice, we confirmed a significant increase in body weight and blood pressure, and predominant hypertrophy of the kidneys, and a predominant decrease in capillary density was observed in the ear skin. We also found that there are pericytes with a flat shape that adheres closely to the vascular wall, and those with a relatively three-dimensional shape that stretches the cytoplasm across multiple blood vessels. We obtained data suggesting that the latter type of pericyte is more prevalent in discontinuous areas of capillaries. In addition, we generated Coll4 a1/a2-floxed mice that induce a breakdown of the vascular construction mechanism.

Free Research Field

血管動態生化学、血管発生学、老化

Academic Significance and Societal Importance of the Research Achievements

組織やぺリサイトとの関係性を加味した毛細血管網の機能評価法は確立されていない。毛細血管網は全身の臓器に隈なく張り巡らされており、皮膚の毛細血管は心・腎といった観察が難しく、機能低下が死に直結しやすい臓器の毛細血管網の状態を反映している可能性が高い。皮膚と他臓器間における毛細血管網異常の相関性が見つかれば、将来的に非侵襲的な皮膚での毛細血管網評価によって危険性が高い他の臓器の疾患予備軍を早期発見できる技術に繋がる可能性がある。安価で安全で簡易的な検査方法の開発は世界的規模で切望されており、本研究の成果は学術的にも診断・治療法の開発にも資する基盤を提供する。