ZC3H4 mediates silica-induced EndoMT via ER stress and autophagy

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.

Automated summary

The study revealed that ZC3H4 plays a regulatory role in silica-induced EndoMT, mediating the process through ER stress and autophagy. This suggests that ZC3H4 may serve as a potential novel target for pulmonary fibrosis treatment.