Coal dust exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis and Vitamin D remedies
| Autor: | Hangbing Cao, Min Mu, Liang Yuan, Xinrong Tao, Huihui Tao, Haoming Chen, Deyong Ge, Yuanjie Zou, Qixian Sun, Dong Hu, Yajun Zhang, Wenyang Wang, Bing Li, Jianhua Wang |
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| Rok vydání: | 2022 |
| Předmět: |
Pulmonary Fibrosis
Health Toxicology and Mutagenesis Epithelial cells Coal dust Toxicology complex mixtures Single-cell RNA sequencing Mice RA1190-1270 medicine Vitamin D and neurology Animals Alveolar regeneration Vitamin D Adaptor Proteins Signal Transducing Chemistry Pneumoconiosis Research Reproducibility of Results Dust General Medicine HD7260-7780.8 medicine.disease Coal Mining respiratory tract diseases Coal dust pulmonary disease Coal Toxicology. Poisons Immunology Macrophage subset phenotype activation Industrial hygiene. Industrial welfare Pulmonary toxicity |
| Zdroj: | Particle and Fibre Toxicology Particle and Fibre Toxicology, Vol 19, Iss 1, Pp 1-21 (2022) |
| ISSN: | 1743-8977 |
| DOI: | 10.1186/s12989-022-00449-y |
| Popis: | Background Coal dust particles (CDP), an inevitable by-product of coal mining for the environment, mainly causes coal workers’ pneumoconiosis (CWP). Long-term exposure to coal dust leads to a complex alternation of biological processes during regeneration and repair in the healing lung. However, the cellular and complete molecular changes associated with pulmonary homeostasis caused by respiratory coal dust particles remain unclear. Methods This study mainly investigated the pulmonary toxicity of respirable-sized CDP in mice using unbiased single-cell RNA sequencing. CDP (< 5 μm) collected from the coal mine was analyzed by Scanning Electron Microscope (SEM) and Mass Spectrometer. In addition, western blotting, Elisa, QPCR was used to detect gene expression at mRNA or protein levels. Pathological analysis including HE staining, Masson staining, immunohistochemistry, and immunofluorescence staining were performed to characterize the structure and functional alternation in the pneumoconiosis mouse and verify the reliability of single-cell sequencing results. Results SEM image and Mass Spectrometer analysis showed that coal dust particles generated during coal mine production have been crushed and screened with a diameter of less than 5 µm and contained less than 10% silica. Alveolar structure and pulmonary microenvironment were destroyed, inflammatory and death (apoptosis, autophagy, and necrosis) pathways were activated, leading to pneumoconiosis in post 9 months coal dust stimulation. A distinct abnormally increased alveolar type 2 epithelial cell (AT2) were classified with a highly active state but reduced the antimicrobial-related protein expression of LYZ and Chia1 after CDP exposure. Beclin1, LC3B, LAMP2, TGF-ß, and MLPH were up-regulated induced by CDP, promoting autophagy and pulmonary fibrosis. A new subset of macrophages with M2-type polarization double expressed MLPH + /CD206 + was found in mice having pneumoconiosis but markedly decreased after the Vitamin D treatment. Activated MLPH + /CD206 + M2 macrophages secreted TGF-β1 and are sensitive to Vitamin D treatment. Conclusions This is the first study to reconstruct the pathologic progression and transcriptome pattern of coal pneumoconiosis in mice. Coal dust had obvious toxic effects on lung epithelial cells and macrophages and eventually induced pulmonary fibrosis. CDP-induced M2-type macrophages could be inhibited by VD, which may be related to the alleviation of the pulmonary fibrosis process. |
| Databáze: | OpenAIRE |
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