Coal dust exposure triggers heterogeneity of transcriptional profiles in mouse pneumoconiosis and Vitamin D remedies

Abstract

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.

Inflammation and fibrosis in the coal dust-exposed lung described by confocal Raman spectroscopy

“…Coal dust particles were collected in a coal mine in Anhui Province, China. The distribution of the particle size and the microelement content were analyzed in our previous study ( Mu et al, 2022 ).…”

“…A CWP mouse model was established via the nasal inhalation of coal dust particles. The murine model was reported previously ( Mu et al, 2022 ). Briefly, 20 mice were randomly divided into two groups: a control group (NS) and a coal dust exposure group.…”

Understanding the pathogenesis of occupational coal and silica dust-associated lung disease

“…Nevertheless, findings from inhalation studies have been used to show the potential effects of different levels and types of coal mining dust exposure on lung disease. M u et al [ 102 ] intranasally challenged C57BL/6 male mice with coal dust for different durations of time (3, 6 and 9 months) and showed that mice challenged with dust showed structural destruction of lung parenchyma with increased inflammation and upregulation of necrotic, autophagic and apoptotic pathways, which led to cell death and eventually lung fibrosis. These results show that coal dust inhalation in mice can be used to recapitulate key pathological features of CWP and thus is an appropriate platform for understanding the mechanisms of disease pathogenesis.…”

Geochemical and Morphological Evaluations of Organic and Mineral Aerosols in Coal Mining Areas: A Case Study of Santa Catarina, Brazil

“…Several studies have previously signaled that transitional elements such as bioavailable iron or nickel are culpable for the incidence of severe health problems [13][14][15][16]. However, the precise chemical nature and compositional information about the materials inhaled in coal mining areas remain scanty [17][18][19]. This knowledge gap is mainly because most published works on coal and potentially hazardous elements (PHEs) geochemistry focus on the toxic emissions and residues produced during combustion in coal power plants [19,20].…”

“…However, the precise chemical nature and compositional information about the materials inhaled in coal mining areas remain scanty [17][18][19]. This knowledge gap is mainly because most published works on coal and potentially hazardous elements (PHEs) geochemistry focus on the toxic emissions and residues produced during combustion in coal power plants [19,20].…”