CircHECTD1 mediates pulmonary fibroblast activation via HECTD1
Chu, Wang, Luo, Zhang, Cheng, Huang, Wang, Dai, Fang, Chao (2019) CircHECTD1 mediates pulmonary fibroblast activation via HECTD1 Ther Adv Chronic Dis (IF: 3.5) 10 2040622319891558
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Abstract
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.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.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.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.© The Author(s), 2019.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887829http://www.ncbi.nlm.nih.gov/pubmed/31832126
http://dx.doi.org/10.1177/2040622319891558
