Schistosoma japonicum soluble egg antigens induce apoptosis and inhibit activation of hepatic stellate cells: a possible molecular mechanism.
Hepatic stellate cells play a key role in the development of hepatic fibrosis. Activated hepatic stellate cells can be reversed to a quiescent-like state or apoptosis can be induced to reverse fibrosis. Some studies have recently shown that Schistosoma mansoni eggs could suppress the activation of hepatic stellate cells and that soluble egg antigens from schistosome eggs could promote immunocyte apoptosis. Hence, in this study, we attempt to assess the direct effects of Schistosoma japonicum soluble egg antigens on hepatic stellate cell apoptosis, and to explore the mechanism by which the apoptosis of activated hepatic stellate cells can be induced by soluble egg antigens, as well as the mechanism by which hepatic stellate cell activation is inhibited by soluble egg antigens. Here, it was shown that S. japonicum-infected mouse livers had increased apoptosis phenomena and a variability of peroxisome proliferator-activated receptor γ expression. Soluble egg antigens induce morphological changes in the hepatic stellate cell LX-2 cell line, inhibit cell proliferation and induce cell-cycle arrest at the G1 phase. Soluble egg antigens also induce apoptosis in hepatic stellate cells through the TNF-related apoptosis-inducing ligand/death receptor 5 and caspase-dependent pathways. Additionally, soluble egg antigens could inhibit the activation of hepatic stellate cells through peroxisome proliferator-activated receptor γ and the transforming growth factor β signalling pathways. Therefore, our study provides new insights into the anti-fibrotic effects of S. japonicum soluble egg antigens on hepatic stellate cell apoptosis and the underlying mechanism by which the liver fibrosis could be attenuated by soluble egg antigens.
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China. Electronic address: yinongduan@gmail.com.
Yinong
Y
Duan
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Xijuan
X
Gu
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Dandan
D
Zhu
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Wei
W
Sun
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Jinling
J
Chen
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Jinrong
J
Feng
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Ke
K
Song
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Feifan
F
Xu
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Xue
X
He
Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
Xingxin
X
He
D000818:Animals; D000947:Antigens, Helminth; D017209:Apoptosis / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D055166:Hepatic Stellate Cells / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D006790:Host-Parasite Interactions / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010063:Ovum / Q000276:immunology; D047495:PPAR gamma / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D012549:Schistosoma japonicum / Q000276:immunology* / Q000472:pathogenicity*; D012554:Schistosomiasis japonica / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000947:Antigens, Helminth; D047495:PPAR gamma; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505640:Tnfrsf10b protein, mouse; C505654:Tnfsf10 protein, mouse; D016212:Transforming Growth Factor beta; C505409:Casp3 protein, mouse; D053148:Caspase 3
Activation; Apoptosis; Hepatic fibrosis; Hepatic stellate cells; Schistosoma japonicum; Soluble egg antigen