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Updated: Jul 26, 2026
Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
Published on: October 28, 2022
Annexin A5 promotes macrophage activation and contributes to pulmonary fibrosis induced by silica particles
1Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Objective:
To investigate the contributions and underlying molecular mechanisms of annexin A5 toward silica-induced pulmonary fibrosis.
Methods:
Male C57BL/6 mice were randomly divided into three groups and instilled intratracheally with silica, saline, or air. Mice were euthanized at 3, 7, 14, or 28 days following treatment. Annexin A5 levels in serum and lung tissues were detected by enzyme-linked immunosorbant assay (ELISA) assays or Western blots. The association of annexin A5 levels with silica-induced lung fibrosis was further investigated in the macrophage cell line, RAW264.7. Following exposure of these cells to silica at a concentration of 200 μg/ml for 6 or 12 h, the expression levels of transforming growth factor β1 (TGF-β1), interleukin 1α (IL-1α), Fas ligand (FasL), and their downstream targets were evaluated by Western blots. Furthermore, annexin A5 and FasL were knocked down by small interfering ribonucleic acid (siRNA) and TGF-β1 secretion into the cell culture medium was measured by ELISA assays or Western blots.
Results:
Mice treated with silica demonstrated lung fibrosis at 28 days following exposure, whereas, in controls, only mild and transient inflammation was evident at day 3 and day 7 postinstillation and was not present at day 14. Furthermore, silica-exposed mice exhibited significantly (p < 0.05) elevated levels of annexin A5 in serum and lung tissues, relative to control groups. Consistent with these findings, silica exposure of RAW264.7 cells for 6 or 12 h, led to an annexin A5-dependent increase in the expression levels of TGF-β1, IL-1α, FasL, and their downstream target molecules. These silica-induced changes were reversed by siRNA-mediated knockdown of annexin A5, but downregulation of FasL led to increased annexin A5 expression and reduced levels of TGF-β1, IL-1α, and FasL downstream target molecules.
Conclusions:
These findings define a role of annexin A5 in promoting macrophage activation via Fas/FasL pathways in silica-induced lung fibrosis.
Insights
Annexin A5 promotes silica-induced lung fibrosis by activating macrophages through Fas/FasL pathways. Reducing annexin A5 levels reversed fibrosis markers in a mouse model, highlighting its therapeutic potential.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Silica exposure is a known cause of pulmonary fibrosis.
- The molecular mechanisms driving silica-induced lung fibrosis are not fully understood.
Purpose of the Study:
- To investigate the role of annexin A5 in silica-induced pulmonary fibrosis.
- To elucidate the underlying molecular mechanisms involving annexin A5.
Main Methods:
- Mice were exposed to silica, and annexin A5 levels were measured in serum and lung tissue.
- Macrophage cell lines (RAW264.7) were exposed to silica to assess annexin A5-dependent changes in fibrosis-related molecules (TGF-β1, IL-1α, FasL).
- Small interfering RNA (siRNA) was used to knock down annexin A5 and FasL to evaluate their specific roles.
Main Results:
- Silica exposure induced lung fibrosis in mice and elevated annexin A5 levels.
- In macrophages, silica exposure increased annexin A5, TGF-β1, IL-1α, and FasL expression.
- Knockdown of annexin A5 reversed silica-induced changes, while FasL downregulation increased annexin A5.
Conclusions:
- Annexin A5 plays a significant role in promoting macrophage activation in silica-induced lung fibrosis.
- The Fas/FasL pathway is implicated in annexin A5-mediated macrophage activation.
- Annexin A5 represents a potential therapeutic target for pulmonary fibrosis.
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