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全反式维甲酸(all-trans retinoic acid,ATRA)诱导细胞分化与上调转录因子Krüppel样因子4(KLF4)表达有关,但目前对ATRA诱导KLF4表达的分子机制尚不清楚.为了研究ATRA在血管平滑肌细胞(VSMC)中诱导KLF4表达的分子机制,本研究观察ATRA对视黄酸受体α(retinoicacid receptorα,RARα)和KLF4表达的影响及RARα介导ATRA诱导KLF4表达所依赖的信号转导途径.实验结果显示,ATRA可显著诱导RARα和KLF4表达,用RARα拮抗剂Ro 41-5253阻断ATRA与受体相互作用后,ATRA诱导的KLF4表达受到显著抑制.用p38 MAPK、ERK和Akt抑制剂阻断ATRA与RARα相互作用所激活的信号转导途径后,发现阻断p38 MAPK信号途径显著抑制ATRA诱导的KLF4表达,抑制ERK信号途径使ATRA对KLF4表达的诱导作用明显增强,抑制Akt信号途径不影响KLF4基因表达.表明RARα介导ATRA对KLF4表达的诱导作用,ATRA通过抑制ERK和激活p38 MAPK信号途径发挥其对KLF4基因表达的诱导作用.
All-trans retinoic acid (ATRA) -induced cell differentiation is related to the up-regulation of KLF4 expression, but the molecular mechanism of ATRA-induced KLF4 expression remains unclear. In order to investigate the role of ATRA in the vascular This study was to investigate the effect of ATRA on the expression of retinoic acid receptorα (RARα) and KLF4 and the signal transduction pathway by which RARα mediates ATRA-induced KLF4 expression The results showed that ATRA could significantly induce the expression of RARα and KLF4, and the ATRA-induced KLF4 expression was significantly inhibited by the interaction of ATRA and RARα antagonist Ro 41-5253.Using p38 MAPK, ERK and Akt inhibitor After blocking the signal transduction pathway activated by the interaction of ATRA and RARα, it was found that blocking the p38 MAPK signaling pathway significantly inhibited the ATRA-induced KLF4 expression and inhibiting the ERK signaling pathway. The induction of ATRA on KLF4 expression was significantly enhanced and the Akt signaling pathway was inhibited Does not affect KLF4 gene expression.It is shown that RARα mediates the induction of KLF4 expression by ATRA and that ATRA exerts its effect on KLF4 gene expression by inhibiting ERK and activating the p38 MAPK signaling pathway use.