| First Author | Shu YN | Year | 2015 |
| Journal | J Mol Cell Cardiol | Volume | 84 |
| Pages | 191-9 | PubMed ID | 25937534 |
| Mgi Jnum | J:319087 | Mgi Id | MGI:6862660 |
| Doi | 10.1016/j.yjmcc.2015.04.020 | Citation | Shu YN, et al. (2015) SM22alpha inhibits vascular inflammation via stabilization of IkappaBalpha in vascular smooth muscle cells. J Mol Cell Cardiol 84:191-9 |
| abstractText | Smooth muscle (SM) 22alpha, an actin-binding protein, is down-regulated in atherosclerotic arteries. Disruption of SM22alpha promotes arterial inflammation through activation of reactive oxygen species (ROS)-mediated nuclear factor (NF)-kappaB pathways. This study aimed to investigate the mechanisms by which SM22alpha regulates vascular inflammatory response. The ligation injury model of SM22alpha(-/-) mice displayed up-regulation of inflammatory molecules MCP-1, VCAM-1, and ICAM-1 in the carotid arteries. Similar results were discovered in human atherosclerotic samples. In vitro studies, overexpression of SM22alpha attenuated TNF-alpha-induced IkappaBalpha phosphorylation and degradation, accompanied by decreased NF-kappaB activity and reduced inflammatory molecule expression. Using coimmunoprecipitation, we found that SM22alpha interacted with and stabilized IkappaBalpha in quiescent VSMCs. Upon TNF-alpha stimulation, SM22alpha was phosphorylated by casein kinase (CK) II at Thr139, leading to dissociation of SM22alpha from IkappaBalpha, followed by IkappaBalpha degradation and NF-kappaB activation. Our findings demonstrate that SM22alpha is a phosphorylation-regulated suppressor of IKK-IkappaBalpha-NF-kappaB signaling cascades. SM22alpha may be a novel therapeutic target for human vascular diseases and other inflammatory conditions. |
