Development of tissue repair treatment for cerebrovascular disease using extracellular matrix protein perlecan

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kyushu University
• Principal Investigator: Nakamura Kuniyuki 九州大学, 大学病院, 助教 (80713742)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ペリサイト / 細胞外マトリックス / 脳梗塞 / 組織修復 / 血液脳関門 / 慢性虚血 / 再髄鞘化

Outline of Final Research Achievements

The purpose of this research project is to clarify the mechanism underlying tissue repair and functional recovery after cerebrovascular diseases. We investigated the tissue repair process in ischemic stroke, focusing on an extracellular matrix (ECM) protein, perlecan, which constitutes the basement membrane. Perlecan was involved in the maintenance of the blood-brain barrier (BBB) and also in the migration of cerebrovascular pericytes around the infarct lesion. Furthermore, we found that pericytes regulated tissue repair through remyelination by oligodendrocyte progenitor cells (OPCs) differentiation and phagocytosis of myelin debris by macrophages. Reciprocal interactions among pericytes, OPCs, macrophages and ECM proteins are important for post-stroke tissue repair and functional recovery.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

脳血管障害はその後遺症によって寝たきりの原因となる大きな要因であり、急性期治療後の機能回復をもたらす治療の開発は重要である。脳は神経だけでなく、血管系、グリアなどの種々の細胞や細胞外マトリックス(ECM)蛋白などから構成される。本研究課題ではECM蛋白perlecanが、脳梗塞後の血液脳関門の維持や脳血管ペリサイトの活性化をもたらし、ペリサイトを起点として組織修復、機能回復が進むことを明らかにした。今回見出した細胞同士、あるいは細胞-ECM間の相互作用および組織修復機序は、脳梗塞治療の新たな分子標的の開発につながる可能性がある。