Research Team Led by Professor Goo Taeg Oh Publishes Article in World’s Top Academic Journal Circulation
- 작성처
- Date2020.11.20
- 9895
(From left) Dr. Sejin Jeon, Prof. Goo Taeg Oh, and Tae Kyeong Kim (PhD candidate)
Professor Goo Taeg Oh (the corresponding author), Dr. Sejin Jeon (the lead author), and PhD candidate Tae Kyeong Kim (second author) from the Department of Life Sciences discovered the athero-protective role of soluble Ninjurin-1 (short for “nerve injury-induced protein 1”, Ninj1) as a novel anti-inflammatory cytokine that is released from alternatively activated macrophages in atherosclerotic plaques. In summary, Ninj1 is a novel MMP9 substrate of plaque macrophages and sNinj1 is a secreted atheroprotective protein that regulates macrophage inflammation and monocyte recruitment in atherosclerosis. Because soluble Ninj1-mediated anti-inflammatory effects are conserved in humans, soluble Ninj1 mimetics could be useful therapies for coronary artery disease. On Tuesday, November 3, the article containing the research findings, titled “Anti-Inflammatory Actions of Soluble Ninjurin-1 Ameliorate Atherosclerosis” was published in Circulation (IF 23.603; Circulation.2020;142:1736-1751).
Atherosclerosis, a chronic inflammatory disease, causes much morbidity and mortality worldwide, including stroke, angina pectoris, myocardial infarction, and sudden cardiac death, which may cause sudden death in severe cases. For the treatment of such vascular diseases, a new method has recently emerged in academia that develops therapeutic agents from antibodies or proteins that regulate the activation of specific factors. In 2001, the research team led by Professor Goo Taeg Oh newly discovered a plasma membrane protein named Ninj1 as a small adhesion molecule related to vascular diseases. His team and collaborators also found that Ninj1 occurs mainly in cancer-related or inflammatory diseases and is involved in cell-to-cell interaction. However, the function and biological relevance of Ninj1 and its soluble form in atherosclerosis remain unknown.
Dr. Sejin Jeon and Tae Kyeong Kim (PhD candidate) from the Department of Life Sciences generated Ninj1 knock-out mouse and Ninj1/Apoe double knout-out mouse as GEMs (genetically engineered mice) made by embryonic stem (ES) cell-based gene targeting technology. Then, they performed atherosclerotic phenotyping in vivo and successfully separated immune cells from single cell suspensions prepared form atherosclerotic aortas of mice for single cell RNA sequencing (scRNA-seq) analysis. scRNA-seq analyses revealed that Ninj1-expressing monocytes and anti-inflammatory macrophages among alternatively activated macrophages and resident macrophages, but not dendritic cells. They found that macrophage Ninj1 was directly cleaved by MMP9 to generate a soluble form (sNinj1) that exhibited anti-atherosclerotic effects, as assessed in vitro and in vivo. Moreover, they revealed that not only treatment with the sNinj1-mimetic peptides inhibited pro-inflammatory functions in human and mouse pro-inflammatory macrophages, but also the continuous administration of them alleviated atherosclerosis by inhibiting the enhanced monocyte recruitment and inflammatory characteristics of this disorder in mice, regardless of the presence of Ninj1.
Professor Goo Taeg Oh commented, “In this study, we present the first in vivo evidence that Ninj1 is a novel MMP9 substrate in macrophages, and further show that its soluble form reduces human and mouse atherosclerosis. Furthermore, we demonstrated soluble Ninj1 has an anti-inflammatory and atheroprotective effect through preclinical studies of mimetic peptides. Our findings highlight the potential of a soluble form of adhesion molecule as a therapeutic target for atherosclerosis treatment. We expect that our findings will be applied in the development of useful therapies for coronary artery disease, as well as in vivo translational research."