scholarly journals Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury

2008 ◽  
Vol 416 (3) ◽  
pp. 337-346 ◽  
Author(s):  
Rafael Mayoral ◽  
Belen Mollá ◽  
Juana Maria Flores ◽  
Lisardo Boscá ◽  
Marta Casado ◽  
...  
Keyword(s):  
Liver Injury ◽  
Transgenic Mice ◽  
Genetic Model ◽  
Acute Liver Injury ◽  
Constitutive Expression ◽  
Transgenic Animals ◽  
Hepatocyte Proliferation ◽  
Nuclear Antigen ◽  
Cox 2 ◽  
Inflammatory Profile

The effect of COX (cyclo-oxygenase)-2-dependent PGs (prostaglandins) in acute liver injury has been investigated in transgenic mice that express human COX-2 in hepatocytes. We have used three well-established models of liver injury: in LPS (lipopolysaccharide) injury in D-GalN (D-galactosamine)-preconditioned mice; in the hepatitis induced by ConA (concanavalin A); and in the proliferation of hepatocytes in regenerating liver after PH (partial hepatectomy). The results from the present study demonstrate that PG synthesis in hepatocytes decreases the susceptibility to LPS/D-GalN or ConA-induced liver injury as deduced by significantly lower levels of the pro-inflammatory profile and plasmatic aminotransferases in transgenic mice, an effect suppressed by COX-2-selective inhibitors. These Tg (transgenic) animals express higher levels of anti-apoptotic proteins and exhibit activation of proteins implicated in cell survival, such as Akt and AMP kinase after injury. The resistance to LPS/D-GalN-induced liver apoptosis involves an impairment of procaspase 3 and 8 activation. Protection against ConA-induced injury implies a significant reduction in necrosis. Moreover, hepatocyte commitment to start replication is anticipated in Tg mice after PH, due to the expression of PCNA (proliferating cell nuclear antigen), cyclin D1 and E. These results show, in a genetic model, that tissue-specific COX-2-dependent PGs exert an efficient protection against acute liver injury by an antiapoptotic/antinecrotic effect and by accelerated early hepatocyte proliferation.

scholarly journals The c-myc proto-oncogene regulates cardiac development in transgenic mice.

1990 ◽  
Vol 10 (7) ◽  
pp. 3709-3716 ◽  
Author(s):  
T Jackson ◽  
M F Allard ◽  
C M Sreenan ◽  
L K Doss ◽  
S P Bishop ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Mrna Expression ◽  
Cardiac Myocyte ◽  
Cellular Proliferation ◽  
Cardiac Development ◽  
Constitutive Expression ◽  
Transgenic Animals ◽  
Hypertrophic Growth ◽  
Myocyte Proliferation

During the maturation of the cardiac myocyte, a transition occurs from hyperplastic to hypertrophic growth. The factors that control this transition in the developing heart are unknown. Proto-oncogenes such as c-myc have been implicated in the regulation of cellular proliferation and differentiation, and in the heart the switch from myocyte proliferation to terminal differentiation is synchronous with a decrease in c-myc mRNA abundance. To determine whether c-myc can influence myocyte proliferation or differentiation, we examined the in vivo effect of increasing c-myc expression during embryogenesis and of preventing the decrease in c-myc mRNA expression that normally occurs during cardiac development. The model system used was a strain of transgenic mice exhibiting constitutive expression of c-myc mRNA in cardiac myocytes throughout development. In these transgenic mice, increased c-myc mRNA expression was found to be associated with both atrial and ventricular enlargement. This increase in cardiac mass was secondary to myocyte hyperplasia, with the transgenic hearts containing more than twice as many myocytes as did nontransgenic hearts. The results suggest that in the transgenic animals there is additional hyperplastic growth during fetal development. However, this additional proliferative growth is not reflected in abnormal myocyte maturation, as assessed by the expression of the cardiac and skeletal isoforms of alpha-actin. The results of this study indicate that constitutive expression of c-myc mRNA in the heart during development results in enhanced hyperplastic growth and suggest a regulatory role for this proto-oncogene in cardiac myogenesis.

The c-myc proto-oncogene regulates cardiac development in transgenic mice

1990 ◽  
Vol 10 (7) ◽  
pp. 3709-3716
Author(s):  
T Jackson ◽  
M F Allard ◽  
C M Sreenan ◽  
L K Doss ◽  
S P Bishop ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Mrna Expression ◽  
Cardiac Myocyte ◽  
Cellular Proliferation ◽  
Cardiac Development ◽  
Constitutive Expression ◽  
Transgenic Animals ◽  
Hypertrophic Growth ◽  
Myocyte Proliferation

During the maturation of the cardiac myocyte, a transition occurs from hyperplastic to hypertrophic growth. The factors that control this transition in the developing heart are unknown. Proto-oncogenes such as c-myc have been implicated in the regulation of cellular proliferation and differentiation, and in the heart the switch from myocyte proliferation to terminal differentiation is synchronous with a decrease in c-myc mRNA abundance. To determine whether c-myc can influence myocyte proliferation or differentiation, we examined the in vivo effect of increasing c-myc expression during embryogenesis and of preventing the decrease in c-myc mRNA expression that normally occurs during cardiac development. The model system used was a strain of transgenic mice exhibiting constitutive expression of c-myc mRNA in cardiac myocytes throughout development. In these transgenic mice, increased c-myc mRNA expression was found to be associated with both atrial and ventricular enlargement. This increase in cardiac mass was secondary to myocyte hyperplasia, with the transgenic hearts containing more than twice as many myocytes as did nontransgenic hearts. The results suggest that in the transgenic animals there is additional hyperplastic growth during fetal development. However, this additional proliferative growth is not reflected in abnormal myocyte maturation, as assessed by the expression of the cardiac and skeletal isoforms of alpha-actin. The results of this study indicate that constitutive expression of c-myc mRNA in the heart during development results in enhanced hyperplastic growth and suggest a regulatory role for this proto-oncogene in cardiac myogenesis.

scholarly journals Resina Draconis Reduces Acute Liver Injury and Promotes Liver Regeneration after 2/3 Partial Hepatectomy in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhi-yong He ◽  
Kai-han Lou ◽  
Jia-hui Zhao ◽  
Ming Zhang ◽  
Lan-chun Zhang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Acute Liver Injury ◽  
Liver Weight ◽  
Nuclear Antigen ◽  
Protective Effects ◽  
Weight Restoration ◽  
Resina Draconis ◽  
Proliferating Cell

Aim. To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. Methods. 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. Results. Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. Conclusion. Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.

Role of CD44 in CTL-induced acute liver injury in hepatitis B virus transgenic mice

2009 ◽  
Vol 44 (3) ◽  
pp. 218-227 ◽  
Author(s):  
Kiminori Kimura ◽  
Masahito Nagaki ◽  
Masanao Saio ◽  
Hisataka Moriwaki ◽  
Kazuhiro Kakimi
Keyword(s):  
Hepatitis B Virus ◽  
Liver Injury ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Acute Liver Injury ◽  
B Virus

scholarly journals Acetaminophen-induced acute liver injury in HCV transgenic mice

2013 ◽  
Vol 266 (2) ◽  
pp. 224-232 ◽  
Author(s):  
Takeki Uehara ◽  
Oksana Kosyk ◽  
Emmanuelle Jeannot ◽  
Blair U. Bradford ◽  
Katherine Tech ◽  
...  
Keyword(s):  
Liver Injury ◽  
Transgenic Mice ◽  
Acute Liver Injury

Liver cancer-related gene CYP2E1 expression in HBV transgenic mice with acute liver injury

Tumor Biology ◽  
2013 ◽  
Vol 35 (4) ◽  
pp. 3671-3677 ◽  
Author(s):  
Chun Zhang ◽  
Qin Wei ◽  
Tao Jiang ◽  
Xi Shou ◽  
Zhi-Qiang Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Cancer ◽  
Transgenic Mice ◽  
Acute Liver Injury ◽  
Related Gene ◽  
Cancer Related Gene ◽  
Cyp2e1 Expression

scholarly journals Steatosis and intrahepatic lymphocyte recruitment in hepatitis C virus transgenic mice

2004 ◽  
Vol 85 (6) ◽  
pp. 1509-1520 ◽  
Author(s):  
Tonino Alonzi ◽  
Chiara Agrati ◽  
Barbara Costabile ◽  
Carla Cicchini ◽  
Laura Amicone ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transgenic Mice ◽  
Core Protein ◽  
Large Fraction ◽  
Constitutive Expression ◽  
Hepatocyte Proliferation ◽  
Phenotypic Analysis ◽  
Western Blots

To assess the effects of constitutive hepatitis C virus (HCV) gene expression on liver, transgenic mice carrying the entire HCV open reading frame inserted in the α1 antitrypsin (A1AT) gene were generated. Expression of A1AT/HCV mRNA was found to be mainly limited to perivascular areas of the liver as indicated by in situ hybridization analysis. HCV core protein was detected in Western blots of liver extracts, whereas the expression of E2, NS3 and NS5 proteins was revealed by immunostaining of liver samples using HCV-specific antisera. Histological analysis of HCV transgenic mice showed that these animals develop extensive steatosis, but very little necrosis of liver tissue. Moreover, a consistent T cell infiltrate and a slight hepatocyte proliferation were observed. Phenotypic analysis of cells infiltrating the liver indicated that recruitment and/or expansion of residing CD8+, NK, NKT and γ δ T cells occurred in transgenic animals. Among these cells, a large fraction of CD8+ T lymphocytes released mainly IL-10 and, to a lesser extent, IFN-γ upon mitogenic stimulation in vitro. Furthermore, both intrahepatic lymphocytes and splenocytes did not produce cytokines in response to HCV antigens. Thus, these data indicate that constitutive expression of HCV proteins may be responsible for intrahepatic lymphocyte recruitment in absence of viral antigen recognition. This response is likely to be driven by virus-induced cellular factors and may play a significant role in the immunopathology of chronic HCV infection and liver disease.

scholarly journals Metabonomic Profiling in Study Protective Effect of Sea Buckthorn Sterol on Acute Liver Injury Induced By Carbon Tetrachloride in Rats

2021 ◽  
Author(s):  
Changting Sheng ◽  
Yang Guo ◽  
Jing Ma ◽  
Eun-Kyung Hong， ◽  
Benyin Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Aspartic Acid ◽  
Acute Liver Injury ◽  
Sea Buckthorn ◽  
Control Group ◽  
Expression Levels ◽  
Cox 2 ◽  
Liver Tissues

Abstract Objective: To study the effect and protection mechanism of sea buckthorn sterol on acute liver injury induced by carbon tetrachloride (CCl4) in rats. Methods: CCl4 was used to make a rat model of acute liver injury. The rats were divided into six groups including blank control group, model control group, bifendate treated positive control group, low-, medium-, and high-doses of sea buckthorn sterol treated groups. The enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), gamma-glutamyl transpeptidase (γ-GT), and catalase (CAT) were investigated. Total antioxidant capacity (T-AOC), total protein (TP), and the content of malondialdehyde (MDA), the level of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in liver tissues were determined. HE staining was used for the observation of inflammatory changes of liver tissues. The endoplasmic reticulum and mitochondria in liver tissues were observed by electron microscope. Wide range of targeted technologies were used for the detection of the full-spectrum metabolome, and metabolome differences among samples were investigated by means of the combination of UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis. Transcriptomics were studied using the RNA-SEQ method. Based on comparison results, gene expression levels were analyzed, and differentially expressed genes were identified according to their expression levels in different samples. Results: After the treatment of sea buckthorn sterol, the activities of SOD, GSH-Px, CAT, T-AOC, and TP in liver tissues were increased, while the activities of γ-GT, COX-2, and PGE2 were decreased, and the content of MDA was also reduced. Sea buckthorn sterol can reduce the inflammatory lesions in liver tissues, and the damage of the structure of endoplasmic reticulum and mitochondria of liver cells were significantly alleviated compared with the model group. The levels of L-malic acid, 7Z, 10Z, 13Z, 16Z, 19Z-docosapentaenoic acid, creatine, N-acetyl-l-alanine, N-acetyl-aspartic acid, trigonelline, 4-guanidine butyric acid, N-amidine L-aspartic acid, CE(16:1), CE(18:2), PE(16:1/16:0), DG(16:0/18:02/0:0), TG(14:0/18:0/20:4), TG(16:0/18:0/20:4), TG(16:0/16:1/22:5), N-glycine-l-leucine, and FFA(6:0) were significantly restored after the treatment of sea buckthorn sterol. Sea buckthorn sterol could participate in the citric acid cycle, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, niacin and niacinamide metabolism, fat digestion and absorption, and glycerophospholipid metabolism. Besides, the expressions of Cyp1a1, Noct, and Tubb6 could be regulated by sea buckthorn sterol, and thus the metabolic damage by CCl4 was reduced. Conclusion: Sea buckthorn sterol could improve liver function in the animal model of CCl4-induced acute liver injury in rats. The mechanism of liver protection is likely related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of inflammatory response.

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