EndMT contributes to the formation of pulmonary vascular endothelial lesion in PAH

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K19101
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Chiba University
• Principal Investigator: Nishimura Rintaro 千葉大学, 大学院医学研究院, 特任助教 (00756091)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 肺動脈性肺高血圧症 / 内皮間葉転換

Outline of Final Research Achievements

Endthelial to mesenchymal transition (EndMT) is defined as the acquisition of mesenchymal characteristics by the endothelium. It has been implicated in pathogenesis and progression of pulmonary arterial hypertension (PAH).
Exposure to Sugen/Hypoxia induced cell proliferation and expression of progenitor cell markers such as CD133 in pulmonary vascular endothelial cells (PVECs) . Moreover, partial EndMT cells (SMA+/CD31+CD45-) were significantly increased in this model compared with hypoxic mice, although complete EndMT cells which lose characteristics of PVECs were confirmed equally in both models. The partial EndMT cells represent feature of progenitor cells prominently. These cells could contribute to the pathogenesis of PAH, especially in intimal lesion.

Free Research Field

肺循環疾患

Academic Significance and Societal Importance of the Research Achievements

現在の肺動脈性肺高血圧症(PAH)の治療薬は過剰な肺血管収縮を標的とした肺血管拡張薬であるが、肺血管を構成する細胞群の異常増殖や形質変化に伴う機能不全が病態形成に深く関与し、新たな治療標的となり得る。
内皮間葉転換(EndMT)は間葉系細胞の供給源として作用するのみではないと考えられる。PAHにおいてEndMTが直接的な間葉系細胞増殖に寄与するのか、機能的に作用しAngiogenesis等を誘導するのかを検討することで、内膜病変を中心としたPAHの病態メカニズムが明らかになり、ひいては新規治療法の開発に結び付くことが期待できる