| First Author | Luo Y | Year | 2016 |
| Journal | Circ Res | Volume | 118 |
| Issue | 6 | Pages | 944-56 |
| PubMed ID | 26838785 | Mgi Jnum | J:256773 |
| Mgi Id | MGI:6099412 | Doi | 10.1161/CIRCRESAHA.115.307674 |
| Citation | Luo Y, et al. (2016) NSun2 Deficiency Protects Endothelium From Inflammation via mRNA Methylation of ICAM-1. Circ Res 118(6):944-56 |
| abstractText | RATIONALE: Vascular endothelial inflammation, including the expression of intercellular adhesion molecule 1 (ICAM-1), is a key event in vascular diseases. However, the mechanisms underlying the regulation of ICAM-1 are largely unknown. OBJECTIVE: To investigate the mechanisms on the regulation of ICAM-1 by NOP2/Sun domain family, member 2 (NSun2)-mediated mRNA methylation and the impact of NSun2-ICAM-1 regulatory process in vascular inflammation and allograft arteriosclerosis. METHODS AND RESULTS: By using in vitro, in cells, and in vivo methylation assays, we showed that the tRNA methyltransferase NSun2 methylated the ICAM-1 mRNA. Methylation by NSun2 promoted the translation of ICAM-1, thereby increasing the adhesion of leukocytes to endothelial cells. Tumor necrosis factor-alpha or homocysteine activated the methyltransferase activity of NSun2 by repressing the phosphorylation of NSun2 by Aurora-B. The levels of ICAM-1 induction and of leukocyte adhesion to vascular endothelium observed with homocysteine treatment in wild-type rats were markedly decreased in NSun2(-/-) rats. In a rat model of aortic allograft, the lack of donor NSun2 impaired the formation of allograft arteriosclerosis. CONCLUSIONS: NSun2 upregulates the expression of ICAM-1 by methylating ICAM-1 mRNA. This regulatory process impacts on vascular inflammation and allograft arteriosclerosis. |
