The role of LPCAT2 in ashma

• Project/Area Number: 17K16043
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: TARUI MEGUMI 東京大学, 保健・健康推進本部, 助教 (40727749)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 気管支喘息 / 炎症性メディエーター

Outline of Final Research Achievements

Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid mediator, which induces a smooth muscle cell contraction. Lysophosphatidylcholine acyltransferase (LPCAT)2 biosynthesizes PAF, and this is activated by PAF itself. We hypothesized that the inhibition of the PAF biosynthetic activity by LPCAT2 provided a novel target for the regulation of inflammatory disorders including bronchial asthma.
We showed the inhibition of LPCAT2 using micro-RNA suppressed the activation of smooth muscle cells. However, using ovalbumin (OVA)-induced allergic asthma model in LPCAT2 deficient transgenic mice, it was not statistically significant that the lack of LPCAT2 suppressed asthma induction.

Academic Significance and Societal Importance of the Research Achievements

気管支喘息は死に至ることのある疾患である。気管支喘息の治療薬は、近年の分子標的薬の発展が目覚ましいが、一方で、病態については未だ解明されていなことも多い。そのためコントロール不良な重症喘息で治療に難渋する人も多い。新しい分子を検討することは、気管支喘息の機序に迫り、補助的治療薬としての可能性につながると考えられる。