A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism
| Autor: | Eva Csizmadia, Maria B. Arvelo, Shane T. Grey, Soizic Daniel, Salvatore T. Scali, Christopher R. Longo, David W. Sun, Virendra I. Patel, Gautam V. Shrikhande, Christiane Ferran |
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| Rok vydání: | 2005 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
medicine.medical_specialty medicine.medical_treatment Cell Cycle Proteins Inflammation Biology Mice Fulminant hepatic failure immune system diseases hemic and lymphatic diseases Internal medicine medicine Animals Hepatectomy Regeneration Tumor Necrosis Factor alpha-Induced Protein 3 Cell Proliferation Hepatology Regeneration (biology) Intracellular Signaling Peptides and Proteins Nuclear Proteins Proteins Zinc Fingers Recovery of Function Survival Analysis Liver regeneration Liver Regeneration Cysteine Endopeptidases Endocrinology medicine.anatomical_structure Liver Apoptosis Hepatocyte Models Animal Hepatocytes Cancer research Liver function medicine.symptom Liver Failure |
| Zdroj: | Hepatology. 42:156-164 |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.20741 |
| Popis: | The liver has a remarkable regenerative capacity, allowing recovery following injury. Regeneration after injury is contingent on maintenance of healthy residual liver mass, otherwise fulminant hepatic failure (FHF) may arise. Understanding the protective mechanisms safeguarding hepatocytes and promoting their proliferation is critical for devising therapeutic strategies for FHF. We demonstrate that A20 is part of the physiological response of hepatocytes to injury. In particular, A20 is significantly upregulated in the liver following partial hepatectomy. A20 protects hepatocytes from apoptosis and ongoing inflammation by inhibiting NF-kappaB. Hepatic expression of A20 in BALB/c mice dramatically improves survival following extended and radical lethal hepatectomy. A20 expression in the liver limits hepatocellular damage hence maintains bilirubin clearance and the liver synthetic function. In addition, A20 confers a proliferative advantage to hepatocytes via decreased expression of the cyclin-dependent kinase inhibitor p21(waf1). In conclusion, A20 provides a proliferative advantage to hepatocytes. By combining anti-inflammatory, antiapoptotic and pro-proliferative functions, A20-based therapies could be beneficial in prevention and treatment of FHF. |
| Databáze: | OpenAIRE |
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