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To investigate the role of the potential pathogenic molecule MMP14 in silicosis.
18 SPF male C57 mice were randomly divided into control and silicosis group, and 16 human specimens from the pneumoconiosis cohort of the Fourth Hospital of West China, Sichuan University. Single-cell sequencing analysis was used to identify differentially expressed genes. A silicosis mouse model was induced by silica dioxide using a non-exposure tracheal instillation method. Hematoxylin-eosin staining and Masson staining were employed to assess the degree of inflammation and fibrosis in mouse lung tissues. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to verify the expression of MMP14 and N-cadherin in the lung tissues. Knockdown of MMP14 in epithelial cells (16HBE) was achieved by small interfering RNA, to further verify the expression of N-cadherin. Cell wound healing assays were used to assess the cell migration after MMP14 knockdown.
MMP14 being selected as a potential pathogenic molecule by single-cell sequencing analysis. Compared with the normal control group, the expression of MMP14 and N-cadherin in silicosis lung tissues was significantly increased 3.78 and 2.42 times, respectively (P<0.001). Knockdown of MMP14 in 16HBE cells stimulated by SiO2 led to the downregulation of N-cadherin by about 30% (P<0.001) and inhibition of cell migration, which area was reduced by 50% (P<0.001).
MMP14 activates the expression of N-cadherin, regulates the epithelial-mesenchymal transition (EMT) process, and promotes silica-induced pulmonary fibrosis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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