Microsomal Prostaglandin E Synthase-1/PGE2 axis induces recovery from ischemia via recruitment of regulatory Tregs

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Kitasato University
• Principal Investigator: Amano Hideki 北里大学, 医学部, 教授 (60296481)
• Co-Investigator(Kenkyū-buntansha): 江島 耕二 北里大学, 医学部, 准教授 (30327324) ; 北里 英郎 北里大学, 医療衛生学部, 教授 (90195256)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 虚血改善 / PGE2 / mPGES-1 / 制御性T細胞 / TGF-beta

Outline of Final Research Achievements

It is well known that immune cells play important role in angiogenesis in ischemic tissues. Recently, we revealed that COX-2-derived PGE2 induces granulation formation by promoting accumulation of regulatory T cell(Tregs).This result prompted us to evaluate the precise mechanism of recovery from ischaemia with respect to the mPGES-1/PGE2 axis, especially by focusing on Tregs in ischemic hind limb model.
Compared to wild-type mice(WT),recovery from ischaemia was suppressed in microsomal prostaglandin E synthase-1 -deficient mice (mPges-1－/－).The number of accumulated Tregs in ischaemic muscle tissue was decreased in mPges-1－/－ mice compared with that in WT mice.The number of accumulated Tregs and blood flow recovery were suppressed when Tregs were depleted by injecting antibody against FR 4 in WT mice but not in mPges-1－/－ mice. These findings suggested that mPGES-1/PGE2 induced neovascularization from ischaemia by promoting the accumulation of Tregs.

Free Research Field

薬理学、循環薬理学、脂質mediator

Academic Significance and Societal Importance of the Research Achievements

飲食の欧米化や高齢化により虚血性心疾患や末梢動脈疾患の患者が増加している。これらに対する経皮的動脈形成術やバイパス術などが確立されているが,中には治療困難例があり,血管新生療法が注目されている。今回、申請者の研究はmPGES-1/PGE2経路を介した虚血改善に制御性T細胞の関与を明らかにした。虚血筋組織周囲へのPGE2及び制御性T細胞の局所投与が虚血性心疾患や閉塞性動脈硬化症の治療薬の開発につながる可能性がある。今後治療薬につながるようより詳細なメカニズムの検討が必要である。