title: Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway.
abstract: Liver fibrosis was viewed as a reversible process. The activation of hepatic stellate cells (HSCs) is a key event in the process of liver fibrosis. The induction of senescence of HSCs would accelerate the clearance of the activated HSCs. Previously, we demonstrated that soluble egg antigens (SEA) of Schistosoma japonicum promoted the senescence of HSCs via STAT3/P53/P21 pathway. In this paper, our study was aimed to explore whether there are other signaling pathways in the process of SEA-induced HSCs aging and the underlying effect of SKP2/P27 signal on senescent HSCs.
  
  
  
  Human hepatic stellate cell line, LX-2 cells, were cultured and stimulated with SEA. Western blot and cellular immunofluorescence analysis were performed to determine the expression of senescence-associated protein, such as P27, SKP2 and FoxO3a. Besides, RNA interfering was applied to knockdown the expression of related protein. The senescence of HSCs was determined by senescence-associated β-gal staining. We found that SEA increased the expression of P27 protein, whereas it inhibited the expression of SKP2 and FoxO3a. Knockdown of P27 as well as overexpression of SKP2 both suppressed the SEA-induced senescence of HSCs. In addition, the nuclear translocation of FoxO3a from the nucleus to the cytoplasm was induced by SEA stimulation.
  
  
  
  The present study demonstrates that SEA promotes HSCs senescence through the FoxO3a/SKP2/P27 pathway.
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Yinong
authors.identifier: 0000-0001-5824-5762
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, People's Republic of China.|Department of Pathogen Biology and Immunology, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, 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, 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, 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, People's Republic of China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Liuting
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, People's Republic of China.
authors.forename: Liting
authors.initials: L
authors.lastname: Wu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000947:Antigens, Helminth / Q000502:physiology*; D002460:Cell Line; D016922:Cellular Senescence; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004531:Eggs / Q000032:analysis; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D006801:Humans; D034622:RNA Interference; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D012549:Schistosoma japonicum / Q000276:immunology*; D015398:Signal Transduction; D012995:Solubility
chemical_list: D000947:Antigens, Helminth; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27