S100B promotes injury-induced vascular remodeling through modulating smooth muscle phenotype
S100B promotes injury-induced vascular remodeling through modulating smooth muscle phenotype
复制标题
S100B 通过调节平滑肌表型促进损伤诱导的血管重塑
DOI：
10.1016/j.bbadis.2017.07.002
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发表时间：
2017-11-01
影响因子：
6.2
通讯作者：
Wang, Jia-Ning
中科院分区：
文献类型：
--
作者：
Cao, Teng;Zhang, Lei;Wang, Jia-Ning
S100 B是神经系统损伤的生物标志物，但它是否也参与血管损伤尚不清楚。在本研究中，我们研究了S100 B在损伤后血管重塑中的作用。大鼠颈动脉球囊损伤逐渐诱导新生内膜形成，同时增加新生内膜血管平滑肌（VSMC）和血清中S100 B的表达沿着增殖细胞核抗原（PCNA）的诱导。腺病毒介导的S100 B基因的shRNA转染可抑制PCNA的表达和血管内膜的增生，并抑制PDGF-BB诱导的VSMC增殖和迁移。相反，S100 B的过表达促进VSMC增殖和迁移。机制上，S100 B通过降低收缩蛋白表达改变VSMC表型，这似乎是由NF-κ B活性介导的。S100 B诱导NF-κ B-p65基因转录、蛋白表达和核转位。NF-κ B活性抑制剂阻断NF-κ B活性可逆转S1 L00 B介导的VSMC收缩蛋白下调和VSMC增殖和迁移增加。似乎S100 B至少部分通过晚期糖基化终产物受体（Receptor for Advanced Glycation End products，RECEPTOR）调节NF-κ B表达，因为RECEPTOR抑制剂减弱S100 B介导的NF-κ B启动子活性以及VSMC增殖。最重要的是，S100 B分泌的VSMC损害内皮管形成在体外，和敲低S100 B促进再内皮化的损伤剥脱动脉在体内。这些数据表明，S100 B是一种新的调节血管重塑损伤后，并可能作为一个潜在的生物标志物的血管损伤或治疗增殖性血管疾病的药物靶点。
S100B is a biomarker of nervous system injury, but it is unknown if it is also involved in vascular injury. In the present study, we investigated S100B function in vascular remodeling following injury. Balloon injury in rat carotid artery progressively induced neointima formation while increasing S100B expression in both neointimal vascular smooth muscle (VSMC) and serum along with an induction of proliferating cell nuclear antigen (PCNA). Knockdown of S100B by its shRNA delivered by adenoviral transduction attenuated the PCNA expression and neointimal hyperplasia in vivo and suppressed PDGF-BB-induced VSMC proliferation and migration in vitro. Conversely, overexpression of S100B promoted VSMC proliferation and migration. Mechanistically, S100B altered VSMC phenotype by decreasing the contractile protein expression, which appeared to be mediated by NF-kappa B activity. S100B induced NF-kappa B-p65 gene transcription, protein expression and nuclear translocation. Blockade of NF-kappa B activity by its inhibitor reversed S1L00B-mediated downregulation of VSMC contractile protein and increase in VSMC proliferation and migration. It appeared that S100B regulated NF-kappa B expression through, at least partially, the Receptor for Advanced Glycation End products (RAGE) because RAGE inhibitor attenuated S100B-mediated NF-kappa B promoter activity as well as VSMC proliferation. Most importantly, S100B secreted from VSMC impaired endothelial tube formation in vitro, and knockdown of S100B promoted re-endothelialization of injury-denuded arteries in vivo. These data indicated that S100B is a novel regulator for vascular remodeling following injury and may serve as a potential biomarker for vascular damage or drug target for treating proliferative vascular diseases.