title: MCPIP1 mediates silica-induced cell migration in human pulmonary fibroblasts.
abstract: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lungs initiates an inflammatory cascade that results in fibroblast proliferation and migration followed by fibrosis. According to previous data from our laboratory, monocyte chemotactic protein-1 (MCP-1) plays a critical role in fibroblast proliferation and migration in conventional two-dimensional (2D) monolayer cultures. The present study aimed to explore the downstream cascade of MCP-1 in both 2D and three-dimensional (3D) cell culture models of silicosis. Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following: 1) SiO2 treatment induces expression of MCP-1-induced protein (MCPIP1) in a time- and dose-dependent manner in both 2D and 3D cultures; 2) the MAPK and phosphatidylinositol-3-kinase (PI3K)/Akt pathways are involved in SiO2-induced MCPIP1 expression; and 3) MCPIP1 induction mediates the SiO2-induced increase in cell migration in both 2D and 3D cultures. The effect of MCP-1 in silicosis occurs mainly through MCPIP1, which, in turn, mediates the observed SiO2-induced increase in pulmonary fibroblast migration. However, the time frame for MCPIP1 induction differed between 2D and 3D cultures, indicating that, compared with conventional 2D cell culture systems, 3D culture may be useful for analyses of fibroblast physiology under conditions that more closely resemble in vivo environments. Our study determined the link between fibroblast-derived MCPIP1 and SiO2-induced cell migration, and this finding provides novel evidence of the potential of MCPIP1 in the development of novel therapeutic strategies for silicosis.
authors.affiliation: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu, China;
authors.forename: Haijun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China;
authors.forename: Xiaoniu
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China;
authors.forename: Yusi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu, China;
authors.forename: Shencun
authors.initials: S
authors.lastname: Fang
authors.affiliation: Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu, China;
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China;
authors.forename: Xingang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu, China;
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China; and.
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China; and Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China chaojie@seu.edu.cn.
authors.forename: Jie
authors.identifier: http://orcid.org/0000-0002-7800-3557
authors.initials: J
authors.lastname: Chao
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D012822:Silicon Dioxide / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014157:Transcription Factors; D012822:Silicon Dioxide; D019869:Phosphatidylinositol 3-Kinases; D012260:Ribonucleases; C510646:ZC3H12A protein, human
keywords: 3-dimensional cultures; MCPIP1; migration; pulmonary fibroblast; silicosis