S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Theses (Master's Degree_분자의학 및 바이오제약학과)
The Mechanism of Lysyl-tRNA Synthetase (KRS) in the Control of Macrophage Migration
대식세포의 움직임을 조절하는 Lysyl-tRNA Synthetase (KRS)의 기전연구
- 융합과학기술대학원 분자의학 및 바이오제약학과
- Issue Date
- 서울대학교 융합과학기술대학원
- Lysyl-tRNA synthetase (KRS); macrophage; migration; inhibition; laminin; Pulmonary Arterial Hypertension (PAH)
- 학위논문 (석사)-- 서울대학교 융합과학기술대학원 분자의학 및 바이오제약학과, 2017. 8. 김성훈.
- Over the past few years, knowledge in immunology has been emphasized for the development of novel drugs, because inflammatory responses are deeply involved in life-threatening pathological human diseases unless seemingly unrelated. Although appropriate infiltration of distinct immune cells plays a central role in protecting against pathogens, aberrant trafficking signals by excessive immune responses drive multifactorial pathogenesis. Therefore, the control of immune cell migration has been risen a novel target for treating various human diseases including cardiovascular diseases.
In our previous study, non-canonical function of lysyl-tRNA synthetase (KRS), one of aminoacyl-tRNA synthetase (ARSs), was regarded as an important cancer cell regulator in that KRS translocates to the plasma membrane on laminin (LN) signal, inducing cell migration. However the role of KRS in immune cells is not well understood yet. Here, we demonstrated that KRS plays a crucial role in the progression of pathogenesis via the control of macrophage migration in vitro and in vivo studies. Although translocation of KRS to the plasma membrane in RAW 264.7 cells on LN 421 signal induced macrophage recruitment, the small compound BC-KI-00053, KRS inhibitor, showed a significant decreases in macrophage migration and ameliorated the progression of disease in rat models. Through this work, we provided a molecular basis for better understanding of novel functions of KRS, not only as an important regulator of macrophage migration but also as an effective therapeutic target for human pathologies in the near future.