| First Author | Kawanami D | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 411 |
| Issue | 4 | Pages | 798-803 |
| PubMed ID | 21787749 | Mgi Jnum | J:175777 |
| Mgi Id | MGI:5287311 | Doi | 10.1016/j.bbrc.2011.07.031 |
| Citation | Kawanami D, et al. (2011) Thrombin induces MCP-1 expression through Rho-kinase and subsequent p38MAPK/NF-kappaB signaling pathway activation in vascular endothelial cells. Biochem Biophys Res Commun 411(4):798-803 |
| abstractText | Thrombin has been shown to increase expression of chemokines such as monocyte chemoattractant protein 1 (MCP-1) in endothelial cells, leading to the development of atherosclerosis. However, the precise mechanism of this induction remains unknown. In the present study, we investigated whether the small G protein RhoA, and its effector, Rho-kinase are involved in MCP-1 induction by thrombin in endothelial cells. Y-27632, a specific Rho-kinase inhibitor, potently inhibited MCP-1 induction by thrombin. Y-27632 significantly decreased the chemotactic activity of thrombin-stimulated supernatants of endothelial cells on monocytes. Importantly, fasudil, a specific Rho-kinase inhibitor, attenuated MCP-1 gene expression in the aorta of db/db mice. Y-27632 attenuated thrombin-mediated phosphorylation of p38MAPK and p65, indicating that Rho-kinase mediates thrombin-induced MCP-1 expression through p38MAPK and NF-kappaB activation. Our findings demonstrate that the Rho/Rho-kinase signaling pathway plays a critical role in thrombin-mediated MCP-1 expression and function, and suggest that Rho/Rho-kinase may be an important target in the development of new therapeutic strategies for atherosclerosis. |
