Necroptotic Cell Death in Liver Transplantation and Underlying Diseases: Mechanisms and Clinical Perspective

被引:36
作者
Shi, Shaojun [1 ]
Verstegen, Monique M. A. [1 ]
Mezzanotte, Laura [2 ]
de Jonge, Jeroen [1 ]
Lowik, Clemens W. G. M. [2 ]
van der Laan, Luc J. W. [1 ]
机构
[1] Erasmus MC, Univ Med Ctr, Dept Surg, Wytemaweg 80,Room Na-1008, NL-3015 CN Rotterdam, Netherlands
[2] Erasmus MC, Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands
关键词
NECROSIS-FACTOR-ALPHA; KINASE DOMAIN-LIKE; HEPATIC ISCHEMIA; PROGRAMMED NECROSIS; IMMUNE-RESPONSES; RIPK1; PROTECTS; MURINE MODELS; ACETAMINOPHEN; APOPTOSIS; INHIBITION;
D O I
10.1002/lt.25488
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Cell death is a natural process for the turnover of aged cells, but it can also arise as a result of pathological conditions. Cell death is recognized as a key feature in both acute and chronic hepatobiliary diseases caused by drug, alcohol, and fat uptake; by viral infection; or after surgical intervention. In the case of chronic disease, cell death can lead to (chronic) secondary inflammation, cirrhosis, and the progression to liver cancer. In liver transplantation, graft preservation and ischemia/reperfusion injury are associated with acute cell death. In both cases, so-called programmed cell death modalities are involved. Several distinct types of programmed cell death have been described of which apoptosis and necroptosis are the most well known. Parenchymal liver cells, including hepatocytes and cholangiocytes, are susceptible to both apoptosis and necroptosis, which are triggered by distinct signal transduction pathways. Apoptosis is dependent on a proteolytic cascade of caspase enzymes, whereas necroptosis induction is caspase-independent. Moreover, different from the "silent" apoptotic cell death, necroptosis can cause a secondary inflammatory cascade, so-called necroinflammation, triggered by the release of various damage-associated molecular patterns (DAMPs). These DAMPs activate the innate immune system, leading to both local and systemic inflammatory responses, which can even cause remote organ failure. Therapeutic targeting of necroptosis by pharmacological inhibitors, such as necrostatin-1, shows variable effects in different disease models.
引用
收藏
页码:1091 / 1104
页数:14
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