SM22α suppresses cytokine-induced inflammation and the transcription of NF-κB inducing kinase (Nik) by modulating SRF transcriptional activity in vascular smooth muscle cells.

摘要: Vascular smooth muscle cell (VSMC) phenotypic modulation is characterized by the downregulation of SMC actin cytoskeleton proteins. Our published study shows that depletion SM22α (aka SM22, Transgelin, an binding protein) promotes inflammation in SMCs activating NF-κB signal pathways both cultured VSMCs and response to vascular injury. The goal this investigate underlying molecular mechanisms whereby SM22 suppresses signaling under inflammatory condition. inducing kinase (Nik, aka MAP3K14, activated LTβR) a key upstream regulator pathways. Here, we show overexpression expression NIK its downstream canonical noncanonical VSMC line treated with LTβR agonist. regulates at transcriptional proteasome-mediated post-translational levels depending on culture By qPCR, chromatin immunoprecipitation luciferase assays, found Nik transcription target serum factor (SRF). Although known be expressed cytoplasm, also nucleus where interacts SRF inhibit prototypical regulated genes including c-fos Egr3. Moreover, carotid injury increases Sm22-/- mice, which partially relieved adenovirally transduced SM22. These findings reveal for first time addition cytoplasm regulate proinflammatory NF-kB as modulator during inflammation.