scholarly journals Senescence and cell death in chronic liver injury: roles and mechanisms underlying hepatocarcinogenesis

Oncotarget ◽  
2017 ◽  
Vol 9 (9) ◽  
pp. 8772-8784 ◽  
Author(s):  
Mengchao Xiao ◽  
Wenjian Chen ◽  
Chao Wang ◽  
Yingfu Wu ◽  
Shiwei Zhu ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Injury ◽  
Chronic Liver ◽  
Chronic Liver Injury

Defying death: the hepatocyte's survival kit

2004 ◽  
Vol 107 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Marieke H. SCHOEMAKER ◽  
Han MOSHAGE
Keyword(s):  
Cell Death ◽  
Liver Injury ◽  
Viral Hepatitis ◽  
Cell Survival ◽  
Apoptotic Cell ◽  
Liver Cells ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Cellular Mechanisms ◽  
Protective Mechanisms

Acute liver injury can develop as a consequence of viral hepatitis, drug- or toxin-induced toxicity or rejection after liver transplantation, whereas chronic liver injury can be due to long-term exposure to alcohol, chemicals, chronic viral hepatitis, metabolic or cholestatic disorders. During liver injury, liver cells are exposed to increased levels of cytokines, bile acids and oxidative stress. This results in death of hepatocytes. In contrast, stellate cells become active and are resistant against cell death. Eventually, acute and chronic liver injury is followed by loss of liver function for which no effective therapies are available. Hepatocytes are well equipped with protective mechanisms to prevent cell death. As long as these protective mechanisms can be activated, the balance will be in favour of cell survival. However, the balance between cell survival and cell death is delicate and can be easily tipped towards cell death during liver injury. Therefore understanding the cellular mechanisms controlling death of liver cells is of clinical and scientific importance and can lead to the identification of novel intervention targets. This review describes some of the mechanisms that determine the balance between cell death and cell survival during liver diseases. The strict regulation of apoptotic cell death allows therapeutic intervention strategies. In this light, receptor-mediated apoptosis and mitochondria-mediated cell death are discussed and strategies are provided to selectively interfere with these processes.

Ductular reactions provide a structural biliary network to preserve bile drainage in the CDE-model of hepatocellular chronic liver injury

2017 ◽  
Vol 66 (1) ◽  
pp. S6
Author(s):  
L.-A. Clerbaux ◽  
R. Manco ◽  
N. Van Hul ◽  
R. Español-Suñer ◽  
C. Bouzin ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Bile Drainage

Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis and tumorigenesis

2021 ◽  
Author(s):  
Tetsuo Takehara ◽  
Naoki Mizutani ◽  
Hayato Hikita ◽  
Yoshinobu Saito ◽  
Yuta Myojin ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Injury ◽  
Cell Viability ◽  
Liver Regeneration ◽  
Adaptor Protein ◽  
Chronic Liver ◽  
Hepatocyte Apoptosis ◽  
Chronic Liver Injury ◽  
The Impact

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

scholarly journals CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism

Gut ◽  
2015 ◽  
Vol 65 (7) ◽  
pp. 1175-1185 ◽  
Author(s):  
Annika Wilhelm ◽  
Victoria Aldridge ◽  
Debashis Haldar ◽  
Amy J Naylor ◽  
Christopher J Weston ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Injury ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Chronic Liver ◽  
Chronic Liver Injury

Extracellular vesicles derived from human embryonic stem cell‐MSCs ameliorate cirrhosis in thioacetamide‐induced chronic liver injury

2018 ◽  
Vol 233 (12) ◽  
pp. 9330-9344 ◽  
Author(s):  
Soura Mardpour ◽  
Seyedeh‐Nafiseh Hassani ◽  
Saeid Mardpour ◽  
Forough Sayahpour ◽  
Massoud Vosough ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Injury ◽  
Embryonic Stem Cell ◽  
Extracellular Vesicles ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Chronic Liver ◽  
Chronic Liver Injury

scholarly journals HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis

2018 ◽  
Vol 128 (6) ◽  
pp. 2436-2451 ◽  
Author(s):  
Celine Hernandez ◽  
Peter Huebener ◽  
Jean-Philippe Pradere ◽  
Daniel J. Antoine ◽  
Richard A. Friedman ◽  
...  
Keyword(s):  
Liver Injury ◽  
Chronic Liver ◽  
Chronic Liver Injury
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