PDF(Pubmed)
Abstract：
Vitamin A deficiency (VAD) induced TGF-β hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial-mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-β, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT and furin are induced in VAD rats. Furthermore, furin expression continues to increase much more markedly after treatment of VAD rats with RA. In control rats and cell lines, an acute RA treatment induced a significant increase in furin expression, concomitant with changes in EMT markers. A ChIP assay demonstrated that RA directly regulates furin transcription. These results emphasize the importance of maintaining vitamin A levels within the physiological range since both levels below and above this range can cause adverse effects that, paradoxically, could be similar. The role of furin in EMT is discussed.
摘要：
维生素A缺乏（VAD）诱导TGF-β过度活化和降低肺细胞粘附蛋白的表达，提示维甲酸（RA）信号的破坏导致上皮-间质转化（EMT）。为了阐明肺维生素A状态在EMT中的作用，几个EMT标记和前蛋白转化酶furin的表达，激活TGF-β，在两个实验模型中进行了分析。我们的体内模型包括对照大鼠，VAD大鼠,对照大鼠和VAD大鼠，用RA治疗。对于体外研究，使用RA治疗的人支气管肺泡上皮细胞。我们的数据表明，在VAD大鼠中诱导了EMT和弗林蛋白酶。此外，用RA治疗VAD大鼠后，弗林蛋白酶的表达继续显着增加。在对照大鼠和细胞系中，急性RA治疗诱导了弗林蛋白酶表达的显着增加，伴随着EMT标记的变化。ChIP测定证明RA直接调节弗林蛋白酶转录。这些结果强调了将维生素A水平保持在生理范围内的重要性，因为低于和高于该范围的维生素A水平都会引起不利影响，矛盾的是,可能是相似的。讨论了弗林蛋白酶在EMT中的作用。
