Abstract：
When stimulated, vascular smooth muscle cells (VSMCs) change from a differentiated to a dedifferentiated phenotype. Dedifferentiated VSMCs have a key activity in cardiovascular diseases such as in-stent restenosis. MicroRNAs (miRNAs) have crucial functions in conversion of differentiated VSMCs to a dedifferentiated phenotype. We investigated the activity of miR-411-5p in the proliferation, migration, and phenotype switch of rat VSMCs.Based on a microRNA array assay, miR-411-5p expression was found to be significantly increased in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB). A CCK-8 assay, transwell assay, and scratch test were performed to measure the effect of miR-411-5p on the proliferation and migration of PDGF-BB-treated VSMCs. MiR-411-5p promoted expression of dedifferentiated phenotype markers such as osteopontin and tropomyosin 4 in PDGF-BB-treated VSMCs. Using mimics and inhibitors, we identified the target of miR-411-5p in PDGF-BB-treated VSMCs and found that calmodulin-regulated spectrin-associated protein-1 (CAMSAP1) was involved in the phenotypic switch mediated by PDGF-BB.By inhibiting expression of CAMSAP1, miR-411-5p enhanced the proliferation, migration, and phenotype switch of VSMCs.Blockade of miR-411-5p interaction with CAMSAP1 is a promising approach to treat in-stent restenosis.
摘要：
当受到刺激时，血管平滑肌细胞（VSMC）从分化表型变为去分化表型。去分化VSMC在心血管疾病如支架内再狭窄中具有关键活性。MicroRNAs（miRNA）在分化的VSMC向去分化表型的转化中具有关键功能。我们研究了miR-411-5p在增殖中的活性，迁移,和大鼠VSMC的表型转换。基于microRNA阵列分析，发现miR-411-5p表达在由血小板衍生的生长因子-BB(PDGF-BB)刺激的培养的VSMC中显著增加。CCK-8检测,transwell分析，并进行划痕试验以测量miR-411-5p对PDGF-BB处理的VSMC的增殖和迁移的影响。MiR-411-5p在PDGF-BB处理的VSMC中促进去分化表型标志物如骨桥蛋白和原肌球蛋白4的表达。使用模拟物和抑制剂，我们在PDGF-BB处理的VSMC中鉴定了miR-411-5p的靶标,并发现钙调蛋白调节的血影蛋白相关蛋白1(CAMSAP1)参与PDGF-BB介导的表型转换.miR-411-5p通过抑制CAMSAP1的表达增强细胞增殖,迁移,和VSMC的表型转换。阻断miR-411-5p与CAMSAP1的相互作用是治疗支架内再狭窄的有希望的方法。
