Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis
The inflammatory response induced by fine particulate matter (PM2.5), a common class of air pollutants, is an important trigger for the development of pulmonary fibrosis. However, the specific mechanisms responsible for this phenomenon are yet to be fully understood. To investigate the mechanisms be...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S014765132400143X |
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| author | Siyu Yang Yaochuan Sun Yajun Luo Yingyi Liu Mengyu Jiang Jiayou Li Qibing Zhang Jun Bai |
| author_facet | Siyu Yang Yaochuan Sun Yajun Luo Yingyi Liu Mengyu Jiang Jiayou Li Qibing Zhang Jun Bai |
| author_sort | Siyu Yang |
| collection | DOAJ |
| description | The inflammatory response induced by fine particulate matter (PM2.5), a common class of air pollutants, is an important trigger for the development of pulmonary fibrosis. However, the specific mechanisms responsible for this phenomenon are yet to be fully understood. To investigate the mechanisms behind the onset and progression of lung fibrosis owing to PM2.5 exposure, both rats and human bronchial epithelial cells were subjected to varying concentrations of PM2.5. The involvement of the PPARG/HMGB1/NLRP3 signaling pathway in developing lung fibrosis caused by PM2.5 was validated through the utilization of a PPARG agonist (rosiglitazone), a PPARG inhibitor (GW9662), and an HMGB1 inhibitor (glycyrrhizin). These outcomes highlighted the downregulation of PPARG expression and activation of the HMGB1/NLRP3 signaling pathway triggered by PM2.5, thereby eliciting inflammatory responses and promoting pulmonary fibrosis. Additionally, PM2.5 exposure-induced DNA hypermethylation of PPARG-encoding gene promoter downregulated PPARG expression. Moreover, the DNA methyltransferase inhibitor 5-azacytidine mitigated the hypermethylation of the PPARG-encoding gene promoter triggered by PM2.5. In conclusion, the HMGB1/NLRP3 signaling pathway was activated in pulmonary fibrosis triggered by PM2.5 through the hypermethylation of the PPARG-encoding gene promoter. |
| first_indexed | 2024-03-07T23:07:01Z |
| format | Article |
| id | doaj.art-5e16c97567fc4a2084e3ceba1800fb8b |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-07T23:07:01Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-5e16c97567fc4a2084e3ceba1800fb8b2024-02-22T04:51:33ZengElsevierEcotoxicology and Environmental Safety0147-65132024-03-01272116068Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axisSiyu Yang0Yaochuan Sun1Yajun Luo2Yingyi Liu3Mengyu Jiang4Jiayou Li5Qibing Zhang6Jun Bai7Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 638000, China; Chongqing Nanan District Center for Disease Control and Prevention, Chongqing 400066, ChinaState Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044, ChinaEnvironmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 638000, ChinaEnvironmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 638000, ChinaEnvironmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 638000, ChinaEnvironmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 638000, ChinaDepartment of pharmacy, The Second People’s Hospital of Deyang City, Deyang 618000, China; Corresponding authors.Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 638000, China; Corresponding authors.The inflammatory response induced by fine particulate matter (PM2.5), a common class of air pollutants, is an important trigger for the development of pulmonary fibrosis. However, the specific mechanisms responsible for this phenomenon are yet to be fully understood. To investigate the mechanisms behind the onset and progression of lung fibrosis owing to PM2.5 exposure, both rats and human bronchial epithelial cells were subjected to varying concentrations of PM2.5. The involvement of the PPARG/HMGB1/NLRP3 signaling pathway in developing lung fibrosis caused by PM2.5 was validated through the utilization of a PPARG agonist (rosiglitazone), a PPARG inhibitor (GW9662), and an HMGB1 inhibitor (glycyrrhizin). These outcomes highlighted the downregulation of PPARG expression and activation of the HMGB1/NLRP3 signaling pathway triggered by PM2.5, thereby eliciting inflammatory responses and promoting pulmonary fibrosis. Additionally, PM2.5 exposure-induced DNA hypermethylation of PPARG-encoding gene promoter downregulated PPARG expression. Moreover, the DNA methyltransferase inhibitor 5-azacytidine mitigated the hypermethylation of the PPARG-encoding gene promoter triggered by PM2.5. In conclusion, the HMGB1/NLRP3 signaling pathway was activated in pulmonary fibrosis triggered by PM2.5 through the hypermethylation of the PPARG-encoding gene promoter.http://www.sciencedirect.com/science/article/pii/S014765132400143XPM2.5DNA methylationPulmonary fibrosisPPARG5-Azacytidine；inflammation |
| spellingShingle | Siyu Yang Yaochuan Sun Yajun Luo Yingyi Liu Mengyu Jiang Jiayou Li Qibing Zhang Jun Bai Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis Ecotoxicology and Environmental Safety PM2.5 DNA methylation Pulmonary fibrosis PPARG 5-Azacytidine；inflammation |
| title | Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis |
| title_full | Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis |
| title_fullStr | Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis |
| title_full_unstemmed | Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis |
| title_short | Hypermethylation of PPARG-encoding gene promoter mediates fine particulate matter-induced pulmonary fibrosis by regulating the HMGB1/NLRP3 axis |
| title_sort | hypermethylation of pparg encoding gene promoter mediates fine particulate matter induced pulmonary fibrosis by regulating the hmgb1 nlrp3 axis |
| topic | PM2.5 DNA methylation Pulmonary fibrosis PPARG 5-Azacytidine；inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S014765132400143X |
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