OBJECTIVES In varicose veins, vascular smooth muscle cells (VSMCs) often shows phenotypic transition and abnormal proliferation and migration. Evidence suggests the FOXC2-Notch pathway may be involved in the pathogenesis of varicose veins. Here, this study aimed to explore the role of long non-coding RNA FOXC2-AS1 (FOXC2 antisense RNA 1) in phenotypic transition, proliferation, and migration of varicose vein-derived VSMCs and to explore whether the FOXC2-Notch pathway was involved in this process. METHODS The effect of FOXC2-AS1 on the proliferation and migration of human great saphenous vein smooth muscle cells (SV-SMCs) was analyzed using MTT assay and Transwell migration assay, respectively. The levels of contractile marker SM22α and synthetic marker osteopontin were measured by immunohistochemistry and Western blot to assess the phenotypic transition. RESULTS The human varicose veins showed thickened intima, media and adventitia layers, increased synthetic VSMCs, as well as upregulated FOXC2-AS1 and FOXC2 expression. In vitro assays showed that FOXC2-AS1 overexpression promoted phenotypic transition, proliferation, and migration of SV-SMCs. However, the effect of FOXC2-AS1 overexpression could be abrogated by both FOXC2 silencing and the Notch signaling inhibitor FLI-06. Furthermore, FOXC2-AS1 overexpression activated the Notch pathway by upregulating FOXC2. CONCLUSION FOXC2-AS1 overexpression promotes phenotypic transition, proliferation, and migration of SV-SMCs, at least partially, by activating the FOXC2-Notch pathway.

中文翻译：

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FOXC2-AS1调节人大隐静脉平滑肌细胞的表型转变，增殖和迁移。

目的在静脉曲张中，血管平滑肌细胞（VSMC）通常表现出表型过渡和异常的增殖和迁移。有证据表明，FOXC2-Notch途径可能参与了静脉曲张的发病机制。在这里，本研究旨在探讨长非编码RNA FOXC2-AS1（FOXC2反义RNA 1）在静脉曲张VSMC的表型转化，增殖和迁移中的作用，并探讨FOXC2-Notch途径是否参与其中。这个过程。方法分别采用MTT法和Transwell迁移法分析FOXC2-AS1对人大隐静脉平滑肌细胞（SV-SMCs）增殖和迁移的影响。通过免疫组织化学和蛋白质印迹法测量收缩标志物SM22α和合成标志物骨桥蛋白的水平，以评估表型转变。结果人的静脉曲张显示内膜，中膜和外膜层增厚，合成的VSMC增加以及FOXC2-AS1和FOXC2表达上调。体外测定表明，FOXC2-AS1的过表达促进了SV-SMC的表型转变，增殖和迁移。但是，FOXC2沉默和Notch信号抑制剂FLI-06均可消除FOXC2-AS1过表达的影响。此外，FOXC2-AS1过表达通过上调FOXC2激活了Notch途径。结论FOXC2-AS1的过度表达通过激活FOXC2-Notch途径至少部分促进SV-SMC的表型转化，增殖和迁移。结果人的静脉曲张显示内膜，中膜和外膜层增厚，合成的VSMC增加以及FOXC2-AS1和FOXC2表达上调。体外测定表明，FOXC2-AS1的过表达促进了SV-SMC的表型转变，增殖和迁移。但是，FOXC2沉默和Notch信号抑制剂FLI-06均可消除FOXC2-AS1过表达的影响。此外，FOXC2-AS1过表达通过上调FOXC2激活了Notch途径。结论FOXC2-AS1的过度表达通过激活FOXC2-Notch途径至少部分促进SV-SMC的表型转化，增殖和迁移。结果人的静脉曲张显示内膜，中膜和外膜层增厚，合成的VSMC增加以及FOXC2-AS1和FOXC2表达上调。体外测定表明，FOXC2-AS1的过表达促进了SV-SMC的表型转变，增殖和迁移。但是，FOXC2沉默和Notch信号抑制剂FLI-06均可消除FOXC2-AS1过表达的影响。此外，FOXC2-AS1过表达通过上调FOXC2激活了Notch途径。结论FOXC2-AS1的过度表达通过激活FOXC2-Notch途径至少部分促进SV-SMC的表型转化，增殖和迁移。体外测定表明，FOXC2-AS1的过表达促进了SV-SMC的表型转变，增殖和迁移。但是，FOXC2沉默和Notch信号抑制剂FLI-06均可消除FOXC2-AS1过表达的影响。此外，FOXC2-AS1过表达通过上调FOXC2激活了Notch途径。结论FOXC2-AS1的过度表达通过激活FOXC2-Notch途径至少部分促进SV-SMC的表型转化，增殖和迁移。体外测定表明，FOXC2-AS1的过表达促进了SV-SMC的表型转变，增殖和迁移。但是，FOXC2沉默和Notch信号抑制剂FLI-06均可消除FOXC2-AS1过表达的影响。此外，FOXC2-AS1过表达通过上调FOXC2激活了Notch途径。结论FOXC2-AS1的过度表达通过激活FOXC2-Notch途径至少部分促进SV-SMC的表型转化，增殖和迁移。FOXC2-AS1过表达通过上调FOXC2激活了Notch途径。结论FOXC2-AS1的过度表达通过激活FOXC2-Notch途径至少部分促进SV-SMC的表型转化，增殖和迁移。FOXC2-AS1过表达通过上调FOXC2激活了Notch途径。结论FOXC2-AS1的过度表达通过激活FOXC2-Notch途径至少部分促进SV-SMC的表型转化，增殖和迁移。