Control of cell free DNA in sepsis and its application to gene therapy by microRNA

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18340
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Kansai Medical University
• Principal Investigator: SOEDA Takehiro 関西医科大学, 医学部, 助教 (30739892)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 敗血症

Outline of Final Research Achievements

Co-culture experiment with human macrophages and phorbol myristate acetate stimulated-neutrophils under different glucose concentration was conducted. Changes in ER stress, apoptosis, efferocytosis, their upper stream intracellular pathway of human macrophages, and cell free DNA concentration in culture medium were measured. By gene transfer of microRNA 21 or resolvin administration, efferocytosis was stimulated with decreased expression of PTEN and PDCD4.

Free Research Field

集中治療、麻酔

Academic Significance and Societal Importance of the Research Achievements

健常人にも、血漿中に少量の cfDNA が存在し、その由来は主にアポトーシスした白血球や骨髄細胞の可能性が報告されているが、敗血症病態で、多数の白血球がアポトーシス、ネクローシスや NETosis 等の細胞死をきたすと、多量の DAMPs が血漿中に逸脱して、cfDNA上昇の原因になると考えられている。今まで、間接的にcfDNAの増加と患者予後の相関に関して報告した研究は多数存在するが、cfDNA産生を制御する事で、敗血症治療の可能性を探索する事は、革新的であると考えている。