Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung disease
Objective The study aims to elucidate whether neutrophil extracellular traps (NETs) promote epithelial-mesenchymal transition (EMT) in alveolar epithelial cells via Toll-like receptor 9 (TLR9) signaling,thereby contributing to the development of idiopathic inflammatory myopathy-associated interstiti...
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| Format: | Article |
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Lanzhou University Press
2024-12-01
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| Series: | 生物医学转化 |
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| Online Access: | http://swyxzh.ijournals.cn/swyxzh/article/html/20240411?st=article_issue |
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| author | Feng Yingyue Zhuo Cui Su Qiyan Cui Xi Guo Jin Zhu Jiarui Zhang Sigong |
| author_facet | Feng Yingyue Zhuo Cui Su Qiyan Cui Xi Guo Jin Zhu Jiarui Zhang Sigong |
| author_sort | Feng Yingyue |
| collection | DOAJ |
| description | Objective The study aims to elucidate whether neutrophil extracellular traps (NETs) promote epithelial-mesenchymal transition (EMT) in alveolar epithelial cells via Toll-like receptor 9 (TLR9) signaling,thereby contributing to the development of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD). Methods An experimental autoimmune myositis (EAM) mouse model was used, using histological and serological methods to clearly define the presence of NETs infiltration, EMT phenotypes, and TLR9 activation in IIM-ILD. In vitro, A549 cells were treated with NETs, and methods such as transcriptome sequencing, immunofluorescence, and Western blotting were used to investigate the mechanisms underlying NETs-induced EMT. Results Lung tissues from EAM mice exhibited NETs infiltration, EMT, and activation of TLR9 signaling. In vitro experiments demonstrated that NETs affected A549 cell viability and morphology, activated the TLR9 signaling pathway, and induced EMT. Moreover, NETs upregulated genes associated with inflammation and fibrosis. Notably, TLR9 gene expression was significantly elevated, and the use of a TLR9 inhibitor alleviated EMT. Conclusion NETs-induced EMT may serve as a key pathogenic mechanism in IIM-ILD, with TLR9 signaling playing a key role. Targeting TLR9 signaling may offer a promising therapeutic approach for IIM-ILD. |
| format | Article |
| id | doaj-art-588001b9ab794a55a42eeecf269a7673 |
| institution | Kabale University |
| issn | 2096-8965 |
| language | zho |
| publishDate | 2024-12-01 |
| publisher | Lanzhou University Press |
| record_format | Article |
| series | 生物医学转化 |
| spelling | doaj-art-588001b9ab794a55a42eeecf269a76732025-01-13T07:20:51ZzhoLanzhou University Press生物医学转化2096-89652024-12-0154879510.12287/j.issn.2096-8965.20240411Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung diseaseFeng Yingyue0Zhuo Cui1Su Qiyan2Cui Xi3Guo Jin4Zhu Jiarui5Zhang Sigong6The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 , Gansu, ChinaThe Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 , Gansu, ChinaThe Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 , Gansu, ChinaThe Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 , Gansu, ChinaThe Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030 , Gansu, ChinaCuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou 730030 , Gansu, ChinaDepartment of Rheumatology and Immunology, the Second Hospital & Clinical Medical School,Lanzhou University, Lanzhou 730030 , Gansu, ChinaObjective The study aims to elucidate whether neutrophil extracellular traps (NETs) promote epithelial-mesenchymal transition (EMT) in alveolar epithelial cells via Toll-like receptor 9 (TLR9) signaling,thereby contributing to the development of idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD). Methods An experimental autoimmune myositis (EAM) mouse model was used, using histological and serological methods to clearly define the presence of NETs infiltration, EMT phenotypes, and TLR9 activation in IIM-ILD. In vitro, A549 cells were treated with NETs, and methods such as transcriptome sequencing, immunofluorescence, and Western blotting were used to investigate the mechanisms underlying NETs-induced EMT. Results Lung tissues from EAM mice exhibited NETs infiltration, EMT, and activation of TLR9 signaling. In vitro experiments demonstrated that NETs affected A549 cell viability and morphology, activated the TLR9 signaling pathway, and induced EMT. Moreover, NETs upregulated genes associated with inflammation and fibrosis. Notably, TLR9 gene expression was significantly elevated, and the use of a TLR9 inhibitor alleviated EMT. Conclusion NETs-induced EMT may serve as a key pathogenic mechanism in IIM-ILD, with TLR9 signaling playing a key role. Targeting TLR9 signaling may offer a promising therapeutic approach for IIM-ILD.http://swyxzh.ijournals.cn/swyxzh/article/html/20240411?st=article_issueneutrophil extracellular trapsinflammatory myopathyinterstitial lung diseaseepithelial-mesenchymal transitiontoll-like receptor 9 |
| spellingShingle | Feng Yingyue Zhuo Cui Su Qiyan Cui Xi Guo Jin Zhu Jiarui Zhang Sigong Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung disease 生物医学转化 neutrophil extracellular traps inflammatory myopathy interstitial lung disease epithelial-mesenchymal transition toll-like receptor 9 |
| title | Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung disease |
| title_full | Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung disease |
| title_fullStr | Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung disease |
| title_full_unstemmed | Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung disease |
| title_short | Involvement of Toll -like receptor 9 signaling in neutrophil extracellular traps-induced epithelial-to-mesenchymal transition in myositis-associated interstitial lung disease |
| title_sort | involvement of toll like receptor 9 signaling in neutrophil extracellular traps induced epithelial to mesenchymal transition in myositis associated interstitial lung disease |
| topic | neutrophil extracellular traps inflammatory myopathy interstitial lung disease epithelial-mesenchymal transition toll-like receptor 9 |
| url | http://swyxzh.ijournals.cn/swyxzh/article/html/20240411?st=article_issue |
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