Mechanism of pathogenesis targeting macrophages and mesothelial cells in an iron chloride-induced pulmonary fibrosis model

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22917
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: Chiba University
• Principal Investigator: Mikami Hideki 千葉大学, 大学院医学研究院, 特任助教 (90876898)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 肺高血圧証 / マクロファージ / 単核球

Outline of Final Research Achievements

As a treatment for pulmonary arterial hypertension (PAH), pulmonary vasodilation therapy is performed in contrast to improve the condition. However, the onset / establishment mechanism of pulmonary hypertension has not been clarified, and further pathological analysis is required to search for new treatment strategies. Mononuclear cell-derived macrophages infiltrate around PAH blood vessels. Suppression of mobilization of mononuclear macrophages into the lung has been reported to improve PAH pathology, suggesting the involvement of bone marrow mononuclear cells in PAH pathology.
In order to explore the possibility of involvement of bone marrow mononuclear exosomes in PAH pathogenesis, we started by creating PAH diseased mice, but we could not create diseased animals and carried out the expected experiment.

Free Research Field

肺高血圧証

Academic Significance and Societal Importance of the Research Achievements

肺動脈性肺高血圧症(PAH)の治療として、病態改善のために肺血管拡張療法が対照的に施行されている。しかし、肺高血圧症の発症/成立機序は明確になっておらず、新規治療戦略探索のためには、さらなる病態解析が必要である。PAH血管周囲には単核球由来マクロファージ・マスト細胞・樹状細胞といった様々な炎症性細胞が浸潤している。その中でも単核球由来マクロファージの肺内への動員抑制はPAH病態を改善させると報告されており、PAH病態における骨髄単核球の関与が示唆されており、その為PAHにおける骨髄単核球関与を解明する必要がある。