白杨素抑制血小板源性生长因子诱导的血管平滑肌细胞迁移和表型转换
投稿时间:2015-06-15  修订日期:2015-06-15  点此下载全文
引用本文:严玲,廖正凯,关红菁,唐其柱.白杨素抑制血小板源性生长因子诱导的血管平滑肌细胞迁移和表型转换[J].医学研究杂志,2016,45(1):25-28
DOI: 10.11969/j.issn.1673-548X.2016.01.007
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作者单位E-mail
严玲 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
廖正凯 430071 武汉大学中南医院放化疗科 qztang@whu.edu.cn 
关红菁 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
唐其柱 430060 武汉大学人民医院心内科、武汉大学心血管病研究所、心血管病湖北省重点实验室  
基金项目:国家自然科学基金资助项目(81000095,30800278,81530012);高等学校新教师基金资助项目(200804861048)
中文摘要:目的 研究白杨素对血小板源性生长因子(PDGF)-BB诱导的血管平滑肌细胞(VSMCs)迁移和表型转换的影响及可能的分子机制。方法 采用Transwell小室法评价白杨素对PDGF-BB诱导的VSMCs迁移的影响,Western blot法测定收缩型VSMCs标志蛋白:α-平滑肌肌动蛋白(α-SMA)、平滑肌22α(SM22α)和结蛋白的表达水平,以及AKT和糖原合酶激酶(GSK)3β的总蛋白和磷酸化蛋白水平。结果 20ng/ml PDGF-BB明显促进VSMCs迁移,而12.5μmol/L白杨素预处理能显著抑制PDGF-BB诱导的VSMCs迁移;20ng/ml PDGF-BB显著降低VSMCs中α-SMA、SM22α和结蛋白的蛋白表达水平,而12.5μmol/L白杨素预处理能逆转这些标志蛋白的下调;20ng/ml PDGF-BB显著升高VSMCs中AKT和GSK3β磷酸化表达水平, 12.5μmol/L白杨素预处理几乎完全阻断PDGF-BB诱导的这些信号分子的磷酸化。结论 白杨素显著抑制PDGF-BB诱导的VSMCs迁移,并能阻止PDGF-BB诱导的VSMCs收缩表型向合成表型转换,其机制可能部分与抑制AKT信号通路活化有关。
中文关键词:白杨素  血小板源性生长因子  血管平滑肌细胞  细胞运动  表型转换
 
Effects of Chrysin on Platelet Derived Growth Factor-induced Migration and Phenotypic Switching of Vascular Smooth Muscle Cells
Abstract:Objective To investigate the effects of chrysin on the migration and phenotypic switching of vascular smooth muscle cells (VSMCs) induced by platelet derived growth factor (PDGF)-BB and the possible molecular mechanism. Methods Migration of VSMCs was determined by transwell assay. Western blot was performed using antibodies against the following contractile VSMC markers:α-smooth muscle actin (α-SMA), smooth muscle 22α (SM22α), and desmin. Western blot was also carried out to evaluate total and phosphorylated protein levels of AKT, and glycogen synthase kinase 3β (GSK3β). Results Treatment of VSMCs with PDGF-BB (20ng/mL) significantly increased the number of migrated cells. However, 12.5μmol/L chrysin pretreatment markedly blocked this migration response. The expression levels of α-SMA, SM22α and desmin were significantly reduced in PDGF-BB-stimulated VSMCs. In contrast, 12.5μmol/L chrysin pretreatment reversed the downregulation of these markers. PDGF-BB induced a significant increase in the levels of phosphorylated AKT, and GSK3β. However, the PDGF-BB-induced activation of these signaling molecules was almost completely blocked by 12.5μmol/L chrysin pretreatment. Conclusion Chrysin can suppress the migration of VSMCs induced by PDGF-BB and prevent the phenotypic switching of VSMCs from a "contractile" to a "synthetic" state in response to PDGF-BB. These beneficial effects on VSMCs were at least partly mediated by the inhibition of the AKT signaling pathways.
keywords:Chrysin  Platelet derived growth factor  Vascular smooth muscle cells  Cell movement  Phenotypic switching
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