矽肺
肝X受体
下调和上调
转录组
纤维化
转录因子
过氧化物酶体增殖物激活受体
核受体
受体
生物
医学
细胞生物学
免疫学
病理
内科学
基因表达
基因
生物化学
作者
Wu Yao,Peiyan Yang,Yuanmeng Qi,Luheng Jin,Ahui Zhao,Mingcui Ding,Di Wang,Yiping Li,Changfu Hao
标识
DOI:10.1016/j.scitotenv.2020.141531
摘要
Silicosis, a severe and irreversible form of pulmonary fibrosis (PF) caused by long-term exposure to dust particles in production environments, is the biggest occupational health concern in China and most low-income countries. The transdifferentiation of pulmonary fibroblasts is the terminal event in silicosis, and specific transcription factors (TFs) play a crucial role in this condition. However, the relationship between TF-mediated regulation and silicosis remains unknown. We performed a transcriptomic analysis to elucidate this relationship, and our results revealed that two TFs, EGR2 and BHLHE40, were upregulated and five, i.e., TBX2, NR1H3 (LXRα), NR2F1, PPARG (PPARγ), and EPAS1, were downregulated in activated fibroblasts. Notably, PPARγ and LXRα expression was also decreased in an experimental mouse model of silicosis. The mechanism underlying these changes may involve TGF-β1 secretion from silica-exposed alveolar macrophages, causing PPARγ and LXRα downregulation, which in turn would result in aberrant α-SMA transcription. Our results suggest that LXRα is a potential target for the prevention of silicosis and PF.
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