MiR-200c-3p promotes ox-LDL-induced endothelial to mesenchymal transition in human umbilical vein endothelial cells through SMAD7/YAP pathway.
MiR-200c-3p promotes ox-LDL-induced endothelial to mesenchymal transition in human umbilical vein endothelial cells through SMAD7/YAP pathway.
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DOI：
10.1186/s12576-021-00815-z
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发表时间：
2021-09-15
影响因子：
2.3
通讯作者：
Jiang, Ling
中科院分区：
文献类型：
--
作者：
Mao, Yongzhong;Jiang, Ling
内皮细胞向间质细胞转化（EndMT）参与了动脉粥样硬化（AS）的发生发展。MiR-200 c-3 p与EndMT有关。然而，miR-200 c-3 p在AS中的功能作用在很大程度上仍然未知。在这里，我们证明了miR-200 c-3 p在AS中调节EndMT的关键作用。以高脂饲料喂养ApoE−/−小鼠建立AS小鼠模型，以氧化低密度脂蛋白（ox-LDL）处理人脐静脉内皮细胞（HUVECs）模拟AS细胞模型。实时荧光定量PCR检测ApoE−/−小鼠和HUVECs中miR-200 c-3 p、SMAD 7和雅普的表达。采用罗丹明鬼笔环肽染色和Western blot方法观察细胞形态和EndMT标记物的表达。采用荧光素酶报告基因分析和免疫共沉淀法验证miR-200 c-3 p、SMAD 7和雅普之间的关系。miR-200 c-3 p在ApoE−/−小鼠和ox-LDL处理的HUVEC的主动脉组织中高度表达，SMAD 7和雅普下调。miR-200 c-3 p过表达促进ox-LDL处理的HUVECs从鹅卵石样上皮表型转化为梭形间充质表型。同时，miR-200 c-3 p上调可抑制ox-LDL处理HUVECs后内皮细胞标志物CD 31和vWF的表达，促进间充质细胞标志物α-SMA和vimentin的表达。miR-200 c-3 p通过与SMAD 7的3′非翻译区相互作用抑制SMAD 7和雅普的表达。此外，miR-200 c-3 p通过抑制SMAD 7/雅普通路促进ox-LDL处理的HUVECs中EndMT的表达。本研究表明MiR-200 c-3 p通过SMAD 7/雅普途径促进ox-LDL诱导的内皮细胞EndMT表达，这可能是动脉粥样硬化发生的重要机制。在线版本包含补充材料，可通过10.1186/s12576-021-00815-z获得。
Endothelial to mesenchymal transition (EndMT) participates in the progression of atherosclerosis (AS). MiR-200c-3p has been implicated in EndMT. However, the functional role of miR-200c-3p in AS remains largely unknown. Here, we demonstrated the critical role of miR-200c-3p in regulating EndMT in AS. ApoE−/− mice were fed with high-fat diet to establish AS mouse model, and human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic AS cell model. The expression of miR-200c-3p, SMAD7 and YAP in ApoE−/− mice and HUVECs was detected by quantitative real-time PCR. Rhodamine phalloidin staining and Western blot were performed to observe cell morphology and EndMT marker expression of HUVECs. Luciferase reporter assay and Co-Immunoprecipitation were performed to verify the relationship among miR-200c-3p, SMAD7, and YAP. MiR-200c-3p was highly expressed, and SMAD7 and YAP were down-regulated in the aortic tissues of ApoE−/− mice and ox-LDL-treated HUVECs. MiR-200c-3p overexpression promoted the transformation of ox-LDL-treated HUVECs from cobblestone-like epithelial phenotype to a spindle-like mesenchymal phenotype. Meanwhile, miR-200c-3p up-regulation repressed the expression of endothelial markers CD31 and vWF and promoted the expression of mesenchymal markers α-SMA and vimentin in the ox-LDL-treated HUVECs. MiR-200c-3p inhibited SMAD7 and YAP expression by interacting with 3′ untranslated region of SMAD7. Moreover, miR-200c-3p promoted EndMT in ox-LDL-treated HUVECs by inhibiting SMAD7/YAP pathway. This work demonstrated that MiR-200c-3p promoted ox-LDL-induced EndMT in HUVECs through SMAD7/YAP pathway, which may be important for the onset of atherosclerosis. The online version contains supplementary material available at 10.1186/s12576-021-00815-z.
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