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Target Concepts:
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Query: UMLS:C0037116 (
silicosis
)
1,822
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phagocytosis of silicon dioxide (SiO
2
) into lung cells causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that are present within mammalian cells; however, researchers have not determined whether circRNAs are involved in the pathophysiologic process of
silicosis
. To elucidate the role of these RNAs in SiO
2
-induced inflammation in pulmonary macrophages, we investigated the upstream molecular mechanisms and functional effects of circRNAs on cell apoptosis, proliferation, and migration. Primary cultures of alveolar macrophages from healthy donors and from patients and the RAW264.7 macrophage cell line were used to explore the functions of circZC3H4 RNA in macrophage activation. The experimental results indicated the following: 1) SiO
2
concomitantly increased circZC3H4 RNA expression and increased
ZC3H4
protein levels; 2) circular
ZC3H4
(circZC3H4) RNA and
ZC3H4
protein participated in SiO
2
-induced macrophage activation; and 3) SiO
2
-activated macrophages promoted fibroblast proliferation and migration via the circZC3H4 RNA/
ZC3H4
pathway. The up-regulation of the
ZC3H4
protein was confirmed in tissue samples from patients with
silicosis
. Our study elucidates a link between SiO
2
-induced macrophage activation and the circZC3H4 RNA/
ZC3H4
pathway, thereby providing novel insight into the potential use of
ZC3H4
to develop novel therapeutic strategies for
silicosis
.-Yang, X., Wang, J., Zhou, Z., Jiang, R., Huang, J., Chen, L., Cao, Z., Chu, H., Han, B., Cheng, Y., Chao, J. Silica-induced initiation of circular
ZC3H4
RNA/
ZC3H4
pathway promotes the pulmonary macrophage activation.
...
PMID:Silica-induced initiation of circular ZC3H4 RNA/ZC3H4 pathway promotes the pulmonary macrophage activation. 2940 12
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 SiO
2
-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.
...
PMID:Elk-1 transcriptionally regulates ZC3H4 expression to promote silica-induced epithelial-mesenchymal transition. 3221 30
