Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0037116 (
silicosis
)
1,822
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Phagocytosis of SiO2 into the lung causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Clinical evidence has indicated that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation characterized by the generation of monocyte chemotactic protein 1, which, in turn, induces fibrosis. However, the details of events downstream of monocyte chemotactic protein 1 activity in pulmonary fibroblasts remain unclear. Here, to elucidate the role of p53 in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Experiments using primary cultured adult human pulmonary fibroblasts led to the following results: 1) SiO2 treatment resulted in a rapid and sustained increase in p53 and
PUMA
protein levels; 2) the MAPK and PI3K pathways were involved in the SiO2-induced alteration of p53 and
PUMA
expression; and 3) RNA interference targeting p53 and
PUMA
prevented the SiO2-induced increases in fibroblast activation and migration. Our study elucidated a link between SiO2-induced p53/
PUMA
expression in fibroblasts and cell migration, thereby providing novel insight into the potential use of p53/
PUMA
in the development of novel therapeutic strategies for
silicosis
treatment.
...
PMID:p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis. 2657 41
Following inhalation into the lungs, silica particles are engulfed by alveolar macrophages, which triggers endogenous or exogenous apoptosis signaling pathways. As an inducer of apoptosis, the role of BBC3/
PUMA
(BCL2-binding component 3) in macrophages during
silicosis
remains unknown. Here, we exposed U937 cell-derived macrophages (UDMs) to SiO
2
in vitro to explore the function of BBC3 in SiO
2
-induced disease. We found that SiO
2
induced increased BBC3 expression, as well as macrophage activation and apoptosis. Knockdown of Bbc3 with specific siRNA significantly mitigated the SiO
2
-induced effects. In addition, our results clearly showed increased levels of autophagy in macrophages exposed to SiO
2
. However, inhibition of BBC3 decreased the occurrence of autophagy. Furthermore, we observed that the blockade of autophagy with 3-MA, an autophagy inhibitor, inhibited SiO
2
-induced macrophage activation and apoptosis. In contrast, rapamycin, an autophagy inducer, further enhanced the effects induced by SiO
2
. The conditioned medium from macrophages exposed to SiO
2
promoted the proliferation and migration of fibroblasts, and the inhibition of BBC3/autophagy reduced the effects of the conditioned medium on fibroblasts. In the mouse model of
silicosis
, Bbc3 knockout mice clearly exhibited decreased levels of autophagy and fibrosis progression. These results suggest that downregulation of BBC3 expression may become a novel therapeutic strategy for the treatment of
silicosis
.
...
PMID:BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis. 2827 37
