期刊
CELLULAR SIGNALLING
卷 33, 期 -, 页码 79-85出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2017.02.006
关键词
Hepatic fibrosis; Natural killer cell; Hepatic stellate cell; Senescence; Granule exocytosis
类别
资金
- National Natural Science Foundation of China [31571455, 31401210, 31600653, 81600483, 81270514]
- Natural Science Foundation of Jiangsu Province [BK20140955]
- Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica [JKLPSE 201502]
- Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis. We found that senescent HSC induced by curcumin are susceptible to NK cells killing, due to the increased expression of NK cell activating ligand major histocompatibility complex class I chain -related genes A (MICA) and UL16-binding proteins 2 (ULBP2), but not Poliovirus Receptor (PVR). Further studies displayed that the interaction between NK cells and senescent LX2 cells stimulated granule exocytosis. Moreover, the inhibition of granule exocytosis weakened the cytotoxicity of NM cells and promoted the accumulation of senescent LX2 cells. Therefore, these aggregated data indicated that NM cells mediated clearance of senescent LX2 cells and granule exocytosis could play a protective role in the improvement of liver fibrosis. (C) 2017 Elsevier Inc All rights reserved.
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