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Published on: April 24, 2021
ZC3H4 mediates silica-induced EndoMT via ER stress and autophagy
Rong Jiang1, Lei Han2, Qianqian Gao2
1Department of Clinical Nursing, School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
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.
Insights
ZC3H4 protein significantly influences silica-induced endothelial-mesenchymal transition (EndoMT) in pulmonary fibrosis by regulating endoplasmic reticulum stress and autophagy, offering a potential new therapeutic target.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Toxicology
Background:
- Silicosis involves inflammatory responses and fibroblast activation, leading to pulmonary fibrosis.
- Endothelial-mesenchymal transition (EndoMT) is a critical process generating myofibroblasts in silicosis.
- The role of ZC3H4 in silica-induced EndoMT was previously unknown.
Purpose of the Study:
- To investigate the role of ZC3H4 in silica-induced EndoMT in pulmonary vessels.
- To determine if ZC3H4 is involved in the pathogenesis of silicosis.
Main Methods:
- Established a silicosis animal model by administering SiO2 to C57BL/6 J mice.
- Utilized Western blotting and immunofluorescence to assess pulmonary fibrosis and EndoMT.
- Employed CRISPR/Cas9 to downregulate ZC3H4 and examine its regulatory function in EndoMT.
Main Results:
- SiO2 exposure upregulated ZC3H4 expression in pulmonary vessels.
- ZC3H4 was confirmed to be involved in silica-induced EndoMT.
- ZC3H4 mediated EndoMT through endoplasmic reticulum (ER) stress and autophagy pathways.
Conclusions:
- ZC3H4 plays a significant role in silica-induced EndoMT via ER stress and autophagy.
- ZC3H4 presents a potential novel therapeutic target for treating pulmonary fibrosis in silicosis.
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