Research Paper Volume 11, Issue 13 pp 4654—4671
Ambient particulate matter attenuates Sirtuin1 and augments SREBP1-PIR axis to induce human pulmonary fibroblast inflammation: molecular mechanism of microenvironment associated with COPD
- 1 Ph.D. Program for Aging, College of Medicine, China Medical University, Taichung, Taiwan
- 2 Division of Community and Family Medicine, China Medical University Hospital, Taichung, Taiwan
- 3 Genomics Research Center, Academia Sinica, Taipei, Taiwan
- 4 Pulmonary Medicine, China Medical University Hospital, Taichung, Taiwan
- 5 Department of Social Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- 6 Department of Family Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- 7 National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- 8 Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- 9 Institute of New Drug Development, China Medical University, Taichung, Taiwan
- 10 Integrative Stem Cell Center, China Medical University Hospital, Taichung, Taiwan
- 11 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Received: February 20, 2019 Accepted: June 4, 2019 Published: July 12, 2019
https://doi.org/10.18632/aging.102077How to Cite
Copyright: Tien et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.