title: PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization.
abstract: Protein interacting with C kinase 1 (PICK1) is a scaffolding protein mainly implicated in neurological diseases, however, the function of PICK1 in acute liver injury (ALI) remains unknown. Our study found a dramatical decrease in mRNA and protein levels of PICK1 in liver tissues and isolated Kupffer cells (KCs) from the liver in mice with ALI. Furthermore, pretreatment the mice with ALI with FSC-231, a pharmacological inhibitor of PICK1, could significantly augment inflammatory response. Furthermore, in vitro studies showed that both lipopolysaccharide (LPS) and interferon gamma (IFN-γ) significantly reduced the expression of PICK1, while IL-4 elevated its expression in RAW 264.7 cells. Additionally, over-expression of PICK1 inhibited the expression of M1 biomarkers by suppressing NF-κB activity, and enhanced the expression of M2 biomarkers by promoting STAT6 activity. In contrast, knockdown of PICK1 or FSC-231 pretreatment promoted M1 polarization and suppressed M2 polarization. Besides, caveolin-1 was identified as a potential target gene controlled by PICK1 in RAW 264.7 cells. Mechanistic investigation revealed a dual role of PICK1 in regulating macrophage polarization and implied PICK1 as a potential therapeutic target in ALI.
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xie
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.
authors.forename: Yuanyao
authors.initials: Y
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics; D018797:Cell Cycle Proteins; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D051242:Caveolin 1; D018797:Cell Cycle Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D050800:STAT6 Transcription Factor; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Acute liver injury; Caveolin-1; Kupffer cells; Macrophage polarization; Protein interacting with C kinase 1; RAW 264.7 cells