Elucidation of the relationships between pathogenic substances and DAMPs receptors.

• Project/Area Number: 17K08587
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Shinshu University
• Principal Investigator: Fujita Yoshiko 信州大学, 医学部, 特任講師 (30416218)
• Co-Investigator(Kenkyū-buntansha): 垣野 明美 信州大学, 学術研究院医学系, 助教 (00534637) ; 沢村 達也 信州大学, 学術研究院医学系, 教授 (30243033)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: DAMPs / 受容体 / 心血管 / 血液

Outline of Final Research Achievements

Using DiI-oxidized LDL uptake into cells as an indicator, we screened receptor library by several methods to identify a novel oxidized LDL receptor. We successfully identified three novel receptors that recognize oxidized LDL. We also confirmed the concentration-dependent uptake of oxidized LDL into cells by the expression of these receptors. On the other hand, when comparing the ligand specificities of these three types of uniquely identified receptors additionally to LOX-1, there was a certain overlap in ligand spectrum including oxidized LDL, suggesting these novel oxidized LDL receptors should work as DAMPs receptors. They might have a function related to self-defense mechanisms by recognizing DAMPs.

Academic Significance and Societal Importance of the Research Achievements

生活習慣病の成因には生体防御機構が重要な働きをしているがその全貌は明らかではない。本研究では、生活習慣病の中で重要な働きをすると考えられている酸化LDLを利用することで、生活習慣病側の視点から、新たな生体防御機構の解明を行う端緒を得た。すなわち、生活習慣病の原因物質が作用する可能性がある新規受容体を同定したが、これらは生体を防御する際に機能することが期待される。今後これらの受容体について研究を進めることで、新たな生体防御機構を明らかにできる可能性がある。