title: Soluble egg antigens of Schistosoma japonicum induce senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway.
abstract: Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Recent findings suggest that senescence of activated HSCs might limit the development of liver fibrosis. Based on previously observed anti-fibrotic effects of soluble egg antigens from Schistosoma japonicum in vitro, we hypothesized that SEA might play a crucial role in alleviating liver fibrosis through promoting senescence of activated HSCs. We show here that SEA inhibited expression of α-SMA and pro-collagen I and promoted senescence of activated HSCs in vitro. In addition, SEA induced an increased expression of P-p53 and p21. Knockdown of p53 inhibited the expression of p21 and failed to induce senescence of activated-HSCs. Phosphorylated STAT3 was elevated upon SEA stimulation, while loss of STAT3 decreased the level of p53 and senescence of HSCs. Results from immunoprecipitation analysis demonstrated that SOCS3 might be involved in the SEA-induced senescence in HSCs through its interaction with p53. This study demonstrates the potential capacity of SEA in restricting liver fibrosis through promoting senescence in HSCs. Furthermore, a novel STAT3-p53-p21 pathway might participate in the observed SEA-mediated senescence of HSCs. Our results suggest that SEA might carry potential therapeutic effects of restraining liver fibrosis through promoting senescence.
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, 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 226001, Jiangsu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Orthopedics and Traumatology Center of PLA, The 153rd Central Hospital of People's Liberation Army, Zhengzhou 450042, Henan, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, Jiangsu, 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 226001, Jiangsu, People's Republic of China.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004527:Egg Proteins / Q000378:metabolism*; D005355:Fibrosis; D055166:Hepatic Stellate Cells / Q000502:physiology*; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004527:Egg Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016159:Tumor Suppressor Protein p53