Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
Oxid Med Cell Longev. 2012;2012:496540. doi: 10.1155/2012/496540. Epub 2012 Jan 22.
Repeated cycles of oxidative injury by allylamine in vivo induce a proliferative rat vascular (aortic) smooth muscle cell (vSMC) phenotype characterized by matrix-dependent enhancement of mitogenic sensitivity, changes in cell surface integrin expression, and osteopontin (opn) overexpression. Here, we show that constitutive and mitogen-stimulated NF-κB DNA binding activity is enhanced in allylamine vSMCs. Matrix-specific changes in cellular Rel protein expression were observed in allylamine vSMCs. The NF-κB DNA binding element located at -1943 in the 5'-UTR strongly inhibited opn promoter activity in allylamine vSMCs, and this response was regulated by the extracellular matrix. Constitutive increases in opn promoter activity were only seen when allylamine cells were seeded on a fibronectin substrate, and this response was independent of the NF-κB DNA binding sequence within the regulatory region. Thus, NF-κB functions as a critical regulator of the allylamine-induced proliferative phenotype in vSMCs.
体内丙烯酰胺的反复氧化损伤诱导增殖性大鼠血管（主动脉）平滑肌细胞（vSMC）表型，其特征是基质依赖性有丝分裂原敏感性增强、细胞表面整合素表达变化和骨桥蛋白（opn）过表达。在这里，我们表明丙烯酰胺 vSMC 中组成型和有丝分裂原刺激的 NF-κB DNA 结合活性增强。在丙烯酰胺 vSMC 中观察到细胞 Rel 蛋白表达的基质特异性变化。位于 5'-UTR 中的-1943 处的 NF-κB DNA 结合元件强烈抑制丙烯酰胺 vSMC 中的 opn 启动子活性，并且该反应受细胞外基质调节。只有当丙烯酰胺细胞接种在纤维连接蛋白底物上时，才能观察到 opn 启动子活性的持续增加，并且这种反应独立于调节区域内的 NF-κB DNA 结合序列。因此，NF-κB 作为 vSMC 中丙烯酰胺诱导的增殖表型的关键调节剂。
