title: Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway.
abstract: Liver fibrosis is a serious disease that is characterized by the excess deposition of extracellular matrix (ECM) components. Activated hepatic stellate cells (HSCs) are a major source of ECM and serve as a key regulator in liver fibrogenesis. Inactivation of HSCs is essential for liver fibrotic regression. The present study explores the underlying mechanisms of Schistosoma japonicum egg antigen p40 (Sjp40) promoting senescence in HSCs and antifibrosis. For the first time we report that Sjp40 inhibits the activation and proliferation of an immortalized human HSC line (LX-2 cells) and promotes cellular senescence and cell cycle arrest. Sjp40 through action on the STAT3/p53/p21 pathway triggered cellular senescence, while knockdown of p53 or STAT3 partly restored cell senescence. In addition, Sjp40-induced cellular senescence caused LX-2 cells to be more sensitive to a human NK cell line (YT cells). Together these findings provide novel insights into the mechanism of antifibrosis and may have implications for the development of antifibrosis therapies.
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Caiqun
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lyu
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence; D024042:Collagen Type I / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015801:Helminth Proteins / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012549:Schistosoma japonicum / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000199:Actins; D000947:Antigens, Helminth; D024042:Collagen Type I; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015801:Helminth Proteins; D050796:STAT3 Transcription Factor; D051197:Toll-Like Receptor 4; D016159:Tumor Suppressor Protein p53; C055560:p40 egg antigen, Schistosoma