Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway.
Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway.
复制标题
日本血吸虫卵抗原p40通过激活STAT3/p53/p21通路促进活化肝星状细胞衰老
DOI：
10.1038/cddis.2016.228
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发表时间：
2016-07-28
影响因子：
9
通讯作者：
Duan Y
中科院分区：
文献类型：
--
作者：
Chen J;Xu T;Zhu D;Wang J;Huang C;Lyu L;Hu B;Sun W;Duan Y
肝纤维化是一种严重的疾病，其特征在于细胞外基质（ECM）成分的过度沉积。活化的肝星状细胞（HSC）是ECM的主要来源，并在肝纤维化中起关键调节作用。HSC的失活对于肝纤维化的消退是必不可少的。本研究旨在探讨日本血吸虫卵抗原p40（Sjp 40）促进肝星状细胞衰老及抗肝纤维化的机制。我们首次报道了Sjp 40抑制永生化人HSC系（LX-2细胞）的活化和增殖，并促进细胞衰老和细胞周期停滞。Sjp 40通过作用于STAT 3/p53/p21通路触发细胞衰老，而p53或STAT 3的敲低部分恢复细胞衰老。此外，Sjp 40诱导的细胞衰老导致LX-2细胞对人NK细胞系（YT细胞）更敏感。这些发现为抗纤维化机制提供了新的见解，并可能对抗纤维化疗法的发展产生影响。
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.