Background

Inflammatory reactions induced by alveolar macrophages and excessive fibroblast activation lead to pulmonary fibrosis in silicosis. The endothelial-mesenchymal transition (EndoMT) is a key source of myofibroblasts. ZC3H4 is a member of the CCCH zinc finger protein family that participates in macrophage activation and epithelial mesenchymal transition (EMT). However, whether ZC3H4 is involved in EndoMT in silicosis has not yet been elucidated. Therefore, we conducted further studies into the role of ZC3H4 in silica-induced EndoMT in pulmonary vessels.

Methods

Western blotting and immunofluorescence staining were used to detect the regulatory influences of SiO₂ on pulmonary fibrosis and EndoMT. ZC3H4 was specifically downregulated using CRISPR/Cas9 to explore whether ZC3H4 regulated EndoMT during silicosis. C57BL/6 J mice were administered with SiO₂ via the trachea to establish a silicosis animal model.

Results

1) SiO₂ exposure increased ZC3H4 expression in pulmonary vessels. 2) ZC3H4 was involved in EndoMT induced by silica. 3) ZC3H4 mediated EndoMT via endoplasmic reticulum stress (ER stress) and autophagy.

Conclusions

ZC3H4 greatly affects the progression of SiO₂-induced EndoMT via ER stress and autophagy, which provides the possibility that ZC3H4 may become a novel target in pulmonary fibrosis treatment.

中文翻译：

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ZC3H4通过内质网应激和自噬介导二氧化硅诱导的EndoMT

背景

肺泡巨噬细胞引起的炎症反应和过度的成纤维细胞活化导致矽肺中的肺纤维化。内皮-间质转化（EndoMT）是成肌纤维细胞的关键来源。ZC3H4是CCCH锌指蛋白家族的成员，该家族参与巨噬细胞激活和上皮间质转化（EMT）。但是，尚未阐明ZC3H4是否参与矽肺病的EndoMT。因此，我们对ZC3H4在二氧化硅诱导的肺血管EndoMT中的作用进行了进一步的研究。

方法

免疫印迹和免疫荧光染色用于检测SiO ₂对肺纤维化和EndoMT的调节作用。使用CRISPR / Cas9专门下调了ZC3H4，以探索在矽肺病中ZC3H4是否调节EndoMT。通过气管向C57BL / 6 J小鼠施用SiO ₂以建立矽肺动物模型。

结果

1）SiO ₂暴露增加了肺血管中ZC3H4的表达。2）ZC3H4参与了二氧化硅诱导的EndoMT。3）ZC3H4通过内质网应激（ER应激）和自噬介导EndoMT。

结论

ZC3H4通过ER应力和自噬极大地影响SiO ₂诱导的EndoMT的进程，这提供了ZC3H4可能成为肺纤维化治疗的新靶标的可能性。