Hepatocyte proliferation/growth arrest balance in the liver of mice during E. multilocularis infection: a coordinated 3-stage course
| Autor: | Junhua Wang, Jing Li, Dominique A. Vuitton, Guodong Lü, Georges Mantion, Xiaomei Lu, Renyong Lin, Chuanshan Zhang, Hao Wen |
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| Přispěvatelé: | Institut de Recherche en Communications et en Cybernétique de Nantes ( IRCCyN ), Mines Nantes ( Mines Nantes ) -École Centrale de Nantes ( ECN ) -Ecole Polytechnique de l'Université de Nantes ( Polytech Nantes ), Université de Nantes ( UN ) -Université de Nantes ( UN ) -PRES Université Nantes Angers Le Mans ( UNAM ) -Centre National de la Recherche Scientifique ( CNRS ), WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, Université de Franche-Comté ( UFC ), WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, SERF Unit, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Xinjiang Medical University, Chinese Government, Institut de Recherche en Communications et en Cybernétique de Nantes (IRCCyN), Mines Nantes (Mines Nantes)-École Centrale de Nantes (ECN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Proteomics
MESH : Hepatocytes MESH : Echinococcosis [ SDV.CAN ] Life Sciences [q-bio]/Cancer MESH: Hepatocytes Mice 0302 clinical medicine Gene expression MESH : Cell Proliferation MESH: Animals MESH : Antigens Differentiation MESH: In Situ Nick-End Labeling lcsh:Science MESH: Tumor Suppressor Protein p53 Regulation of gene expression 0303 health sciences MESH : Gene Expression Regulation Intracellular Signaling Peptides and Proteins 3. Good health 030220 oncology & carcinogenesis Disease Progression Medicine MESH: Disease Progression MESH : Carrier Proteins Cyclin-Dependent Kinase Inhibitor p21 MESH : Cyclin-Dependent Kinase Inhibitor p21 MESH: Enzyme Activation MESH : Cyclins Caspase 3 MESH: Carrier Proteins Gastroenterology and Hepatology Echinococcus multilocularis Microbiology MESH: Cyclin-Dependent Kinase Inhibitor p21 03 medical and health sciences MESH: Echinococcosis Cyclins In Situ Nick-End Labeling Biology MESH: Echinococcus multilocularis lcsh:R MESH : Mitogen-Activated Protein Kinases MESH : Disease Progression Enzyme Activation Apoptosis Immunology lcsh:Q Parasitology Carrier Proteins MESH: Female MESH: Liver Necrosis lcsh:Medicine MESH : Models Biological MESH : Echinococcus multilocularis Molecular Cell Biology MESH: Caspase 3 MESH : Female MESH : Caspase 3 Mice Inbred BALB C Multidisciplinary biology Animal Models MESH: Gene Expression Regulation medicine.anatomical_structure Infectious Diseases Liver Hepatocyte MESH: Antigens Differentiation MESH : In Situ Nick-End Labeling Female medicine.symptom Mitogen-Activated Protein Kinases Research Article Neglected Tropical Diseases MESH: Mice Inbred BALB C [SDV.CAN]Life Sciences [q-bio]/Cancer Models Biological Andrology Immune system Model Organisms Echinococcosis Proliferating Cell Nuclear Antigen MESH: Cell Proliferation MESH : Mice medicine Animals MESH: Mice MESH : Mice Inbred BALB C 030304 developmental biology Cell Proliferation MESH: Models Biological MESH : Liver biology.organism_classification MESH: Cyclins Antigens Differentiation MESH: Mitogen-Activated Protein Kinases MESH : Tumor Suppressor Protein p53 MESH: Proliferating Cell Nuclear Antigen Gene Expression Regulation MESH : Proliferating Cell Nuclear Antigen Hepatocytes MESH : Animals Tumor Suppressor Protein p53 MESH : Enzyme Activation |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2012, 7 (1), pp.e30127. 〈10.1371/journal.pone.0030127〉 PLoS ONE, Public Library of Science, 2012, 7 (1), pp.e30127. ⟨10.1371/journal.pone.0030127⟩ PLoS ONE, Vol 7, Iss 1, p e30127 (2012) |
| ISSN: | 1932-6203 |
| Popis: | International audience; BACKGROUND: Alveolar echinococcosis (AE) is characterized by the tumor-like growth of Echinococcus (E.) multilocularis. Very little is known on the influence of helminth parasites which develop in the liver on the proliferation/growth arrest metabolic pathways in the hepatocytes of the infected liver over the various stages of infection. METHODOLOGY/PRINCIPAL FINDINGS: Using Western blot analysis, qPCR and immunohistochemistry, we measured the levels of MAPKs activation, Cyclins, PCNA, Gadd45β, Gadd45γ, p53 and p21 expression in the murine AE model, from day 2 to 360 post-infection. Within the early (day 2-60) and middle (day60-180) stages, CyclinB1 and CyclinD1 gene expression increased up to day30 and then returned to control level after day60; Gadd45β, CyclinA and PCNA increased all over the period; ERK1/2 was permanently activated. Meanwhile, p53, p21 and Gadd45γ gene expression, and caspase 3 activation, gradually increased in a time-dependent manner. In the late stage (day180-360), p53, p21 and Gadd45γ gene expression were significantly higher in infected mice; JNK and caspase 3 were activated. TUNEL analysis showed apoptosis of hepatocytes. No significant change in CyclinE, p53 mRNA and p-p38 expression were observed at any time. CONCLUSIONS: Our data support the concept of a sequential activation of metabolic pathways which 1) would first favor parasitic, liver and immune cell proliferation and survival, and thus promote metacestode fertility and tolerance by the host, and 2) would then favor liver damage/apoptosis, impairment in protein synthesis and xenobiotic metabolism, as well as promote immune deficiency, and thus contribute to the dissemination of the protoscoleces after metacestode fertility has been acquired. These findings give a rational explanation to the clinical observations of hepatomegaly and of unexpected survival of AE patients after major hepatic resections, and of chronic liver injury, necrosis and of hepatic failure at an advanced stage and in experimental animals. |
| Databáze: | OpenAIRE |
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