Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway

被引：45

作者：

Chen, Jinling ^{[1
]}

Xu, Tianhua ^{[1
]}

Zhu, Dandan ^{[1
]}

Wang, Jianxin ^{[2
]}

Huang, Caiqun ^{[1
]}

Lyu, Lei ^{[1
]}

Hu, Bin ^{[1
]}

Sun, Wei ^{[1
]}

Duan, Yinong ^{[1
]}

机构：

[1] Nantong Univ, Sch Med, Dept Pathogen Biol, 19 Qixiu Rd, Nantong 226001, Jiangsu, Peoples R China

[2] Nantong Univ, Lab Med Ctr, Affiliated Hosp, Nantong 226001, Jiangsu, Peoples R China

来源：

CELL DEATH & DISEASE | 2016年 / 7卷

基金：

中国国家自然科学基金;

关键词：

CELLULAR SENESCENCE; LIVER FIBROSIS; NATURAL-KILLER; APOPTOSIS; INTERLEUKIN-10; MECHANISMS; REGRESSION; DIOSCIN; ROLES; SJP40;

D O I：

10.1038/cddis.2016.228

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：e2315 / e2315

页数：11

共 47 条

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