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PM2.5 Activates Sirtuin‐SREBP1‐PIR Axis to Induce Pulmonary Fibroblast Inflammation: A Molecular Mechanism Model of Environmental Factor Induced Lung Fibrosis and COPD
Author(s) -
Tien ChiaPing,
Chang YuChan,
Hung ShihChieh,
Hsiao Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb361
Subject(s) - copd , inflammasome , inflammation , chronic bronchitis , lung , cancer research , sirtuin 1 , sterol regulatory element binding protein , pulmonary fibrosis , immunology , lung cancer , sirtuin , medicine , fibrosis , transcription factor , chemistry , downregulation and upregulation , gene , biochemistry , acetylation
PM2.5 has been shown to have strong link with increased risk in human mortality and morbidity, including bronchitis, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. However, the underlying molecular mechanisms induced by PM2.5 remain unclear. To identify the molecular targets of PM2.5, we analyzed transcriptomics data by microarray chips in human pulmonary fibroblasts (HPF) after exposure to different doses of PM2.5. We have identified candidate genes that may involve in the induction of lung inflammation. Our results showed that the SREBF2 and SREBF1 are the top 2 transcription factors activated in response to PM2.5 exposure in HPF. Our analysis showed that IL‐6 , IL24 , LIF , PIR and HMOX1 were the most significantly downregulated transcriptional targets of SREBF1 . Additionally, SREBP1, was found to be directly deacetylated and inhibited by SIRT1 , as well as increase the expression of inflammasome markers, ex. NLPR3 , ASC , and IL‐1β . Our results further showed that SREBF1 , PIR, and NLRP3 inhibitors were found to reverse PM2.5 induced inflammation. In conclusion, our results identified that SIRT1‐SREBP1‐PIR/NLRP3 inflammasome axis may play a key role in PM2.5‐induced fibroblast‐mediated pulmonary disease and may serve as a new target for therapy to prevent fibrosis and COPD. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .