期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-11303-z
关键词
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资金
- National Science and Technology Key Project [2017ZX10201201, 2017ZX10203201-005, 2017ZX10202203-006-001, 2017ZX10302201-004-002]
- Beijing Municipal Administration of Hospital's Ascent Plan [DFL20151601]
- National Natural Science Foundation of China [31571165]
- Beijing Municipal Science & Technology Commission [Z151100004015066]
- YouAn fund for liver diseases and AIDS [YNKT20160012]
- Basic-Clinical Cooperation Project of Capital Medical University [17JL47]
- Department of Veterans Affairs
- NIH [P01 CA163200, P50 AA11999]
Acute injury in the setting of liver fibrosis is an interesting and still unsettled issue. Most recently, several prominent studies have indicated the favourable effects of liver fibrosis against acute insults. Nevertheless, the underlying mechanisms governing this hepatoprotection remain obscure. In the present study, we hypothesized that macrophages and their M1/M2 activation critically involve in the hepatoprotection conferred by liver fibrosis. Our findings demonstrated that liver fibrosis manifested a beneficial role for host survival and apoptosis resistance. Hepatoprotection in the fibrotic liver was tightly related to innate immune tolerance. Macrophages undertook crucial but divergent roles in homeostasis and fibrosis: depleting macrophages in control mice protected from acute insult; conversely, depleting macrophages in fibrotic liver weakened the hepatoprotection and gave rise to exacerbated liver injury upon insult. The contradictory effects of macrophages can be ascribed, to a great extent, to the heterogeneity in macrophage activation. Macrophages in fibrotic mice exhibited M2-preponderant activation, which was not the case in acutely injured liver. Adoptive transfer of M2-like macrophages conferred control mice conspicuous protection against insult. In vitro, M2-polarized macrophages protected hepatocytes against apoptosis. Together, M2-like macrophages in fibrotic liver exert the protective effects against lethal insults through conferring apoptosis resistance to hepatocytes.
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