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Particulate Matter Activates SIRT1‐SREBP1‐PIR Pathway to Promote Pulmonary Fibroblast Inflammation and Enhance Lung Fibrosis
Author(s) -
Tien Chia-Ping,
Chang Yu-Chan,
Hung Shih-Chieh,
Hsiao Michael
Publication year - 2020
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.2020.34.s1.02829
Subject(s) - inflammasome , sterol regulatory element binding protein , copd , medicine , pathogenesis , nod , inflammation , chronic bronchitis , cancer research , fibrosis , immunology , chemistry , endocrinology , diabetes mellitus , cholesterol , sterol
Particulate matter (PM) is infamous for its strong connection with a variety of human disorders and diseases, including bronchitis, asthma, chronic obstructive pulmonary disease (COPD), cancer, allergy, stroke, Alzheimer’s disease, anxiety, cardiovascular disease, productive dysfunction, anemia, and diabetes. While mechanisms driving PM‐induced pathogenesis are poorly understood, it’s believed associated with PM’s unique character, small size with large surface area, allowing PM easily enters the body with a great amount of toxin attached. In an attempt to identify the microenvironment induced by PM, we treated human pulmonary fibroblasts (HPF) with different doses of PM, and our in vitro results showed that PM activated sterol regulatory element‐binding protein 1 (SREBP1) and its downstream PIRIN (PIR) and Nod‐like receptor protein 3 (NLRP3) inflammasome through downregulating Sirtuin1 (SIRT1). Our further in silico analysis revealed that overexpression of PIR was related to tobacco and consistent with early COPD, while our IHC analysis reported the correlation of PIR with PM from lung tissues of PM‐fed mouse models. Taken together, we concluded that PM caused lung fibrosis and COPD via SIRT1‐SREBP1‐PIR/ NLRP3 inflammasome axis, which may provide several plausible therapeutic targets for PM‐related adverse sequelae. Support or Funding Information This work was supported by grants from Academia Sinica and Ministry of Science and Technology [MOST 104‐0210‐01‐09‐02, MOST 105‐0210‐01‐13‐01, and MOST 106‐0210‐01‐15‐02] to Michael Hsiao.