title: Hepatic stellate cell interferes with NK cell regulation of fibrogenesis via curcumin induced senescence of hepatic stellate cell.
abstract: 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 NK cells and promoted the accumulation of senescent LX2 cells. Therefore, these aggregated data indicated that NK cells mediated clearance of senescent LX2 cells and granule exocytosis could play a protective role in the improvement of liver fibrosis.
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Cardiology, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Hao
authors.affiliation: Class AP, Grade 11, Nanjing NO.1 High School, Nanjing, Jiangsu Province, China.
authors.forename: Shunyu
authors.initials: S
authors.lastname: Yao
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Naqi
authors.initials: N
authors.lastname: Lian
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xingran
authors.initials: X
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Mianli
authors.initials: M
authors.lastname: Bian
authors.affiliation: Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jiangjuan
authors.initials: J
authors.lastname: Shao
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pathology, School of Medicine, Saint Louis University, MO, USA.
authors.forename: Anping
authors.initials: A
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: nytws@163.com.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008813:Mice, Inbred ICR
chemical_list: D003474:Curcumin
keywords: Granule exocytosis; Hepatic fibrosis; Hepatic stellate cell; Natural killer cell; Senescence