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Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy
Haijun Liu1,2, Shencun Fang3, Wei Wang3
1Department of Physiology, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing, Jiangsu, 210009, China.
Background:
Silicosis is characterized by accumulation of fibroblasts and excessive deposition of extracellular matrix. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a critical role in fibrosis induced by SiO2. However, the details of the downstream events of MCPIP1 activity in pulmonary fibrosis remain unclear. To elucidate the role of MCPIP1-induced autophagy in SiO2-induced fibrosis, both the upstream molecular mechanisms and the functional effects of SiO2 on cell apoptosis, proliferation and migration were investigated.
Results:
Experiments using primary cultures of alveolar macrophages from healthy donors and silicosis patients as well as differentiated U937 macrophages demonstrated the following results: 1) SiO2 induced macrophage autophagy in association with enhanced expression of MCPIP1; 2) autophagy promoted apoptosis and activation of macrophages exposed to SiO2, and these events induced the development of silicosis; 3) MCPIP1 facilitated macrophage apoptosis and activation via p53 signaling-mediated autophagy; and 4) SiO2-activated macrophages promoted the proliferation and migration of fibroblasts via the MCPIP1/p53-mediated autophagy pathway.
Conclusions:
Our results elucidated a link between SiO2-induced fibrosis and MCPIP1/p53 signaling-mediated autophagy. These findings provide novel insight into the potential targeting of MCPIP1 or autophagy in the development of potential therapeutic strategies for silicosis.
Insights
Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) and autophagy are key in silicosis development. Targeting MCPIP1/p53-mediated autophagy may offer new therapeutic strategies for silica-induced lung fibrosis.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Toxicology
Background:
- Silicosis involves fibroblast accumulation and excessive extracellular matrix deposition.
- Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is crucial in silica (SiO2)-induced fibrosis.
- Downstream effects of MCPIP1 in pulmonary fibrosis require further elucidation.
Purpose of the Study:
- To investigate the role of MCPIP1-induced autophagy in SiO2-induced fibrosis.
- To explore upstream molecular mechanisms of MCPIP1 activity.
- To determine the functional effects of SiO2 on macrophage apoptosis, proliferation, and migration.
Main Methods:
- Primary alveolar macrophages from healthy donors and silicosis patients were used.
- Differentiated U937 macrophages were utilized for experiments.
- Key molecular pathways including MCPIP1, p53, and autophagy were analyzed.
Main Results:
- SiO2 induced macrophage autophagy and enhanced MCPIP1 expression.
- Autophagy promoted SiO2-induced macrophage apoptosis and activation, contributing to silicosis.
- MCPIP1 facilitated macrophage apoptosis and activation through p53 signaling-mediated autophagy.
- SiO2-activated macrophages promoted fibroblast proliferation and migration via the MCPIP1/p53-mediated autophagy pathway.
Conclusions:
- A link between SiO2-induced fibrosis and MCPIP1/p53 signaling-mediated autophagy was established.
- Findings offer novel insights into targeting MCPIP1 or autophagy for silicosis therapeutics.
- This study provides a basis for developing new therapeutic strategies for silicosis.
