title: Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy.
abstract: 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 SiO2on cell apoptosis, proliferation and migration were investigated.
  
  
  
  Experiments using primary cultures of alveolar macrophages from healthy donors and silicosis patients as well as differentiated U937 macrophages demonstrated the following results: 1) SiO2induced 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.
  
  
  
  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.
authors: Department of Physiology, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing, Jiangsu, 210009, China.|Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
authors: Haijun
authors: H
authors: Liu
authors: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu, 210029, China.
authors: Shencun
authors: S
authors: Fang
authors: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu, 210029, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Physiology, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing, Jiangsu, 210009, China.
authors: Yusi
authors: Y
authors: Cheng
authors: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu, 210029, China.
authors: Yingming
authors: Y
authors: Zhang
authors: Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
authors: Hong
authors: H
authors: Liao
authors: Department of Pharmacology, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing, Jiangsu, 210009, China. yaohh@seu.edu.cn.|Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, 210096, China. yaohh@seu.edu.cn.
authors: Honghong
authors: H
authors: Yao
authors: Department of Physiology, School of Medicine, Southeast University, 87 Dingjiaqiao Rd, Nanjing, Jiangsu, 210009, China. chaojie@seu.edu.cn.|Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, 210096, China. chaojie@seu.edu.cn.|Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China. chaojie@seu.edu.cn.
authors: Jie
authors: 0000-0002-7800-3557
authors: J
authors: Chao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D034741:RNA, Small Interfering / Q000235:genetics; D012260:Ribonucleases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000633:toxicity*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020298:U937 Cells
chemical_list: D034741:RNA, Small Interfering; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012822:Silicon Dioxide; D012260:Ribonucleases; C510646:ZC3H12A protein, human
keywords: Autophagy; MCPIP1; Migration; Silicosis; p53