國家衛生研究院 NHRI:Item 3990099045/12083
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    題名: Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: Molecular mechanism of microenvironment associated with COPD
    作者: Tien, CP;Chen, CH;Lin, WY;Liu, CS;Liu, KJ;Hsiao, M;Chang, YC;Hung, SC
    貢獻者: National Institute of Cancer Research
    摘要: Evidences have shown a strong link between particulate matter (PM) and increased risk in human mortality and morbidity, including asthma, chronic obstructive pulmonary disease (COPD), respiratory infection, and lung cancer. However, the underlying toxicologic mechanisms remain largely unknown. Utilizing PM-treated human pulmonary fibroblasts (HPF) models, we analyzed gene expression microarray data and Ingenuity Pathway Analysis (IPA) to identify that the transcription factor sterol regulatory element-binding protein 1 (SREBP1) was the main downstream regulator of Sirtuin1 (SIRT1). Quantitative PCR and western blot results showed that SIRT1 inhibited SREBP1 and further downregulated Pirin (PIR) and Nod-like receptor protein 3 (NLRP3) inflammasome after PM exposure. Inhibitors of SIRT1, SREBP1, and PIR could reverse PM-induced inflammation. An in silico analysis revealed that PIR correlated with smoke exposure and early COPD. Immunohistochemical analysis of tissue microarrays from PM-fed mouse models was used to determine the association of PIR with PM. These data demonstrate that the SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may be associated with PM-induced adverse health issues. SIRT1 functions as a protector from PM exposure, whereas PIR acts as a predictor of PM-induced pulmonary disease. The SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may present several potential therapeutic targets for PM-related adverse health events.
    日期: 2019-07-12
    關聯: Aging. 2019 Jul 12;11(13):4654-4671.
    Link to: http://dx.doi.org/10.18632/aging.102077
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1945-4589&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000475849100026
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85069487132
    顯示於類別:[劉柯俊] 期刊論文

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