{'fraction_non_alphanumeric': 0.038435140700068635, 'fraction_numerical': 0.017844886753603295, 'mean_word_length': 5.942857142857143, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Protection against Fas‐induced liver apoptosis in transgenic mice expressing cyclooxygenase 2 in hepatocytes

Cyclooxygenase‐2 (COX‐2) is upregulated in many cancers, and the prostanoids synthesized increase proliferation, improve angiogenesis, and inhibit apoptosis in several tissues. To explore the function of COX‐2 in liver, transgenic (Tg) mice were generated containing a fusion gene (LIVhCOX‐2) consisting of human COX‐2 cDNA under the control of the human ApoE promoter. Six lines were developed; all of them expressed the LIVhCOX‐2 transgene selectively in hepatocytes. The Tg mice exhibited a normal phenotype, and the increased levels of PGE2 found were due to the constitutively expressed COX‐2. Histological analysis of different tissues and macroscopic examination of the liver showed no differences between wild‐type (Wt) and Tg animals. However, Tg animals were resistant to Fas‐mediated liver injury, as demonstrated by low levels of plasmatic aminotransferases, a lesser caspase‐3 activation, and Bax levels and an increase in Bcl‐2, Mcl‐1, and xIAP proteins, when compared with the Wt animals. Moreover, the resistance to Fas‐mediated apoptosis is suppressed in the presence of COX‐2–selective inhibitors, which prevented prostaglandin accumulation in the liver of Tg mice. Conclusion: These results demonstrate that expression of COX‐2–dependent prostaglandins exerted a protection against liver apoptosis. (HEPATOLOGY 2007;45:631–638.)