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.
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.
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.