Halofuginone (HF) is an extract from the widely used traditional Chinese medicine (TCM) Dichroa febrifuga that facilitates the recovery of wounds and attenuates hepatic fibrosis. However, the role of HF in the epithelial-mesenchymal transition (EMT) of IPEC-J2 cells remains unclear. The current study explored the anti-EMT effect of HF in IPEC-J2 cells and illustrates its molecular mechanism. Transforming growth factor β1 (TGF-β1), as a recognized profibrogenic cytokine, decreased the level of the epithelial marker E-cadherin and increased the level of the mesenchymal markers, such as N-cadherin, fibronectin (FN), vimentin (Vim), and α-smooth muscle actin (α-SMA), in IPEC-J2 cells depending on the exposure time and dose. HF markedly prevented the EMT induced by TGF-β1. Dissection of the mechanism revealed that HF inhibited IPEC-J2 cell EMT via modulating the phosphorylation of SMAD2/3 and the SMAD2/3-SMAD4 complex nuclear translocation. Furthermore, HF could promote the phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), which modulates the SMAD signaling pathway. These results suggested that HF inhibits TGF-β1-induced EMT in IPEC-J2 cells through the eIF2α/SMAD signaling pathway. Our findings suggest that HF can serve as a potential anti-EMT agent in intestinal fibrosis therapy.

中文翻译：

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eIF2α 参与卤夫酮驱动的 TGF-β1 诱导的 EMT 抑制

Halofuginone (HF) 是一种从广泛使用的中药 (TCM) Dichroa febrifuga 中提取的提取物，可促进伤口恢复并减轻肝纤维化。然而，HF 在 IPEC-J2 细胞上皮间质转化 (EMT) 中的作用仍不清楚。目前的研究探索了 HF 在 IPEC-J2 细胞中的抗 EMT 作用并阐明了其分子机制。转化生长因子 β1 (TGF-β1) 作为公认的促纤维化细胞因子，降低了上皮标志物 E-钙粘蛋白的水平，并增加了间充质标志物的水平，如 N-钙粘蛋白、纤连蛋白 (FN)、波形蛋白 (Vim)和 α-平滑肌肌动蛋白 (α-SMA)，在 IPEC-J2 细胞中取决于暴露时间和剂量。HF 显着阻止了 TGF-β1 诱导的 EMT。对该机制的剖析表明，HF 通过调节 SMAD2/3 的磷酸化和 SMAD2/3-SMAD4 复合核易位来抑制 IPEC-J2 细胞 EMT。此外，HF 可以促进真核翻译起始因子-2α (eIF2α) 的磷酸化，从而调节 SMAD 信号通路。这些结果表明 HF 通过 eIF2α/SMAD 信号通路抑制 IPEC-J2 细胞中 TGF-β1 诱导的 EMT。我们的研究结果表明，HF 可以作为肠道纤维化治疗中潜在的抗 EMT 药物。这些结果表明 HF 通过 eIF2α/SMAD 信号通路抑制 IPEC-J2 细胞中 TGF-β1 诱导的 EMT。我们的研究结果表明，HF 可以作为肠道纤维化治疗中潜在的抗 EMT 药物。这些结果表明 HF 通过 eIF2α/SMAD 信号通路抑制 IPEC-J2 细胞中 TGF-β1 诱导的 EMT。我们的研究结果表明，HF 可以作为肠道纤维化治疗中潜在的抗 EMT 药物。