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Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy
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نویسنده
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liu h. ,fang s. ,wang w. ,cheng y. ,zhang y. ,liao h. ,yao h. ,chao j.
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منبع
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particle and fibre toxicology - 2016 - دوره : 13 - شماره : 1
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چکیده
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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. © 2016 the author(s).
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کلیدواژه
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Autophagy; MCPIP1; Migration; P53; Silicosis
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آدرس
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school of medicine,southeast university,department of physiology,87 dingjiaqiao rd,nanjing,jiangsu,210009,china,china pharmaceutical university,neurobiology laboratory,new drug screening centre,nanjing,jiangsu,210009, China, nanjing chest hospital,nine department of respiratory medicine,nanjing,jiangsu,210029, China, nanjing chest hospital,nine department of respiratory medicine,nanjing,jiangsu,210029, China, school of medicine,southeast university,department of physiology,87 dingjiaqiao rd,nanjing,jiangsu,210009, China, nanjing chest hospital,nine department of respiratory medicine,nanjing,jiangsu,210029, China, china pharmaceutical university,neurobiology laboratory,new drug screening centre,nanjing,jiangsu,210009, China, school of medicine,southeast university,department of pharmacology,87 dingjiaqiao rd,nanjing,jiangsu,210009,china,southeast university,key laboratory of developmental genes and human disease,nanjing,210096, China, school of medicine,southeast university,department of physiology,87 dingjiaqiao rd,nanjing,jiangsu,210009,china,southeast university,key laboratory of developmental genes and human disease,nanjing,210096,china,zhongda hospital,school of medicine,southeast university,department of respiration,nanjing,jiangsu,210009, China
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Authors
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