CircHECTD1 mediates pulmonary fibroblast activation via HECTD1
CircHECTD1 mediates pulmonary fibroblast activation via HECTD1
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DOI：
10.1177/2040622319891558
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发表时间：
2019
影响因子：
3.5
通讯作者：
Jie Chao
中科院分区：
文献类型：
--
作者：
Han Chu;Wei Wang;Wei Luo;Wei Zhang;Yusi Cheng;Jie Huang;Jing Wang;Xiaoniu Dai;Shencun Fang;Jie Chao
所发表的Abstract.Background: Circular RNA (circRNA), a new class of noncoding RNA, has been shown to be important in silicosis due to its unique role as a transcription regulator or as a sponge of small RNA regulators. Here, the mechanisms underlying circHECTD1/HECTD1 in fibroblast activation and subsequent fibrosis induced by SiO2 were investigated. Methods: Primary human pulmonary fibroblasts (HPF-a) were utilized, combined with quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) assays. LC3B-LV-RFP lentivirus was used to evaluate the role of autophagy. The CRISPR/Cas9 system was applied to specifically knock down HECTD1, combined with MTT, BrdU, and migration assays, to explore the functional changes induced by SiO2. Results: After exposure to SiO2, the circHECTD1 level was decreased, which was associated with an increase in HECTD1 in HPF-a cells. SiO2-induced autophagy was reversed by either circHECTD1 overexpression or HECTD1 knockdown in HPF-a cells, with restored SiO2-induced fibroblast activation, proliferation, and migration via downstream autophagy. The lungs of mice exposed to SiO2 confirmed the upregulation of HECTD1 in pulmonary fibroblasts. Conclusions: Our data suggested a link between circHECTD1/HECTD1 and fibroblast activation with subsequent fibrosis induced by SiO2, providing novel insight into the potential of circHECTD1/HECTD1 to be a therapeutic target for silicosis. .中文摘要：