Schistosoma japonicum soluble egg antigens induce apoptosis and inhibit activation of hepatic stellate cells: a possible molecular mechanism
Schistosoma japonicum soluble egg antigens induce apoptosis and inhibit activation of hepatic stellate cells: a possible molecular mechanism
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日本血吸虫可溶性卵抗原诱导肝星状细胞凋亡并抑制肝星状细胞活化：可能的分子机制
DOI：
10.1016/j.ijpara.2013.11.003
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发表时间：
2014-03-01
影响因子：
4
通讯作者：
He, Xingxin
中科院分区：
文献类型：
--
作者：
Duan, Yinong;Gu, Xijuan;He, Xingxin
肝星状细胞在肝纤维化的发展中起关键作用。激活的肝星状细胞可以逆转到静止状态或诱导细胞凋亡来逆转纤维化。近年来有研究表明，曼氏血吸虫卵可抑制肝星状细胞的活化，血吸虫卵可溶性抗原可促进免疫细胞凋亡。因此，本研究旨在探讨日本血吸虫可溶性卵抗原对肝星状细胞凋亡的直接影响，探讨可溶性卵抗原诱导活化的肝星状细胞凋亡的机制，以及可溶性卵抗原抑制肝星状细胞活化的机制。本研究表明，日本血吸虫感染小鼠肝脏细胞凋亡现象增加，过氧化物酶体增殖物激活受体γ表达变异性增加。可溶性卵抗原诱导肝星状细胞LX-2细胞系形态改变，抑制细胞增殖，诱导细胞周期阻滞于G(1)期。可溶性蛋抗原还通过tnf相关的凋亡诱导配体/死亡受体5和caspase依赖途径诱导肝星状细胞凋亡。此外，可溶性蛋抗原可通过过氧化物酶体增殖体激活受体γ和转化生长因子β信号通路抑制肝星状细胞的活化。因此，本研究为日本血吸虫可溶性卵抗原对肝星状细胞凋亡的抗纤维化作用以及日本血吸虫可溶性卵抗原减轻肝纤维化的机制提供了新的认识。(C) 2014澳大利亚寄生虫学学会Elsevier Ltd.出版。版权所有。
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 gamma 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 G(1) 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 gamma and the transforming growth factor beta 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. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.