What is the role of incretin and its degrading enzyme in the pathology of pulmonary hypertension?

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16885
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Hosokawa Susumu 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (00737025)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 肺高血圧症 / DPP-4阻害薬 / GLP-1受容体作動薬 / caveolin-1

Outline of Final Research Achievements

In this study, we investigated the role of GLP-1, which is insulin-stimulating hormone, and DPP-4, which is degrading enzyme, in the pathology of pulmonary hypertension.
In rats with monocrotaline-induced pulmonary hypertension, GLP-1 receptor agonist liraglutide , DPP-4 inhibitor alogliptin, or their combination improved pulmonary hypertension and increased survival rates. As for the mechanism, it was revealed that DPP-4 inhibitor suppresses the inflammatory pathway mediated by NF-kB in pulmonary artery smooth muscle cells through its proteolytic enzyme function. Furthermore, DPP-4 was suggested to be involved in pulmonary artery smooth muscle cell proliferation as T cell activation antigen CD26. On the other hand, regarding GLP-1 receptor agonists, real-time PCR results suggested the involvement of tissue factor.

Free Research Field

肺循環

Academic Significance and Societal Importance of the Research Achievements

肺動脈性肺高血圧症のこれまでの治療は３系統（プロスタサイクリン、エンドセリン、一酸化窒素）が用いられ、いずれも血管拡張作用が主であり、新規治療薬の開発が求められている。本研究では、2型糖尿病治療薬が肺高血圧症動物モデルを改善すること、その機序が炎症に関与するシグナル伝達経路を抑制することで肺血管リモデリングを軽減することを明らかにした。肺高血症の新規治療薬の開発へ向けて、多大な貢献をもたらすものと考える。