期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 529, 期 2, 页码 474-479出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.06.041
关键词
Cell recruitment; Inflammatory responses; HSCs; KCs
资金
- National Natural Science Foundation of China [31871379]
- National Basic Research Program of China 973 Program [2015CB964700]
- Guangdong Province Science and Technology Plan [2018A050506070, 2016B030301007, 2015B020230007, 2014B020225004]
- Guangzhou City Science and Technology Plan [201704020212]
- Chinese Government Recruitment Thousand Talents Program [ODCCC2268]
- UCAS Scholarship for International Ph.D. Students
- CAS-PIFI Post-doctoral Fellowship
- CAS-TWAS President's Fellowship for International Ph.D. students
Currently, there is a growing interest in understanding the cellular and molecular events of immune-cell trafficking and recruitment of hepatic stellate cells (HSCs) in liver diseases. Aberrant activation of HSCs is the key event leading to chronic liver fibrosis. However, the underlying mechanisms of the recruitment of HSCs in a locally injured liver are not clearly understood. Here, we report a new experimental approach for the study of inflammatory responses as well as the recruitment of HSCs into the localized cryolesion. We observed a significant liver damage accompanied by the up-regulation of plasma ALT and AST. In addition, we also found increased levels of MCP-1, IL-6 and IL-10 cytokines. The peak cytokine levels were detected at 8 h after injury, followed by intrahepatic infiltration of neutrophils and monocytes into the injury site (from 8 h to day 3), while the kupffer cells (KCs) and HSCs were mainly detected on day 3 after injury. Interestingly, the depletion of KCs, but not neutrophils, reduced the directional recruitment and accumulation of HSCs at the injury site. Moreover, the combinatorial recruitment of KCs and HSCs resulted in the gradual restoration of fibrotic area to almost typical histological appearance on day 14 post-injury. In conclusion, our data demonstrated a localized infiltration and accumulation of neutrophils and monocytes at a predefined loci, and further revealed that KCs are critical for the recruitment of HSCs during injury, and thus, may play an important role in tissue repair. (C) 2020 Elsevier Inc. All rights reserved.
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