| First Author | Jiang R | Year | 2020 |
| Journal | Lab Invest | Volume | 100 |
| Issue | 7 | Pages | 959-973 |
| PubMed ID | 32218530 | Mgi Jnum | J:298375 |
| Mgi Id | MGI:6472535 | Doi | 10.1038/s41374-020-0419-2 |
| Citation | Jiang R, et al. (2020) Elk-1 transcriptionally regulates ZC3H4 expression to promote silica-induced epithelial-mesenchymal transition. Lab Invest 100(7):959-973 |
| abstractText | The epithelial-mesenchymal transition (EMT) process is a key priming activity of fibroblasts in pulmonary fibrosis during silicosis. Ets-like protein-1 (Elk-1) is a critical modulator that promotes functional changes in cells, and the effects are mediated by oxidative stress (OS). However, whether ELK-1 is involved in EMT of silicosis remains unclear. In addition, researchers have found that Elk-1 is involved in the expression of the gene zc3h12a, which encodes the protein MCPIP1, and MCPIP1 is a member of the zinc finger Cys-Cys-Cys-His (CCCH)-type protein family. A previous study from our lab showed that ZC3H4, which is also a member of the CCCH-type protein family, critically affected the regulation of EMT during silicosis. However, it has not yet been elucidated if ELK-1 acts at the promoter for zc3h4 to increase its expression in a mechanism that is similar to that of the zc3h12a gene and whether such regulation ultimately controls EMT. Therefore, we explored the correlation between ELK-1 and ZC3H4 expression and tested the underlying mechanisms affecting ELK-1 activation induced by silica. Our study identifies that SiO2-mediated EMT via ELK-1, with the upstream activity of OS and the downstream signaling of ZC3H4 expression resulting in enhanced EMT. These findings suggest that the nuclear transcription factor ELK-1 may be useful as a novel target for the treatment of pulmonary fibrosis. |
