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论文题目: Liver-Specific Deletion of SRSF2 Caused Acute Liver Failure and Early Death in Mice
英文论文题目: Liver-Specific Deletion of SRSF2 Caused Acute Liver Failure and Early Death in Mice
第一作者: Cheng, YM; Luo, CL; Wu, WW; Xie, ZQ; Fu, XD; Feng, Y
英文第一作者: Cheng, YM; Luo, CL; Wu, WW; Xie, ZQ; Fu, XD; Feng, Y
联系作者: Feng, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Food Safety Res, Inst Nutr Sci, Shanghai, Peoples R China.
英文联系作者: Feng, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Food Safety Res, Inst Nutr Sci, Shanghai, Peoples R China.
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发表年度: 2016
卷: 36
期: 11
页码: 1628-1638
摘要: The liver performs a variety of unique functions critical for metabolic homeostasis. Here, we show that mice lacking the splicing factor SRSF2 but not SRSF1 in hepatocytes have severe liver pathology and biochemical abnormalities. Histological analyses revealed generalized hepatitis with the presence of ballooned hepatocytes and evidence of fibrosis. Molecular analysis demonstrated that SRSF2 governs splicing of multiple genes involved in the stress-induced cell death pathway in the liver. More importantly, SRSF2 also functions as a potent transcription activator, required for efficient expression of transcription factors mainly responsible for energy homeostasis and bile acid metabolism in the liver. Consistent with the effects of SRSF2 in gene regulation, accumulation of total cholesterol and bile acids was prominently observed in the mutant liver, followed by enhanced generation of reactive oxygen species and increased endoplasmic reticulum stress, as revealed by biochemical and ultrastructural analyses. Taking these observations together, inactivation of SRSF2 in liver caused dysregulated splicing events and hepatic metabolic disorders, which trigger endoplasmic reticulum stress, oxidative stress, and finally liver failure.
英文摘要: The liver performs a variety of unique functions critical for metabolic homeostasis. Here, we show that mice lacking the splicing factor SRSF2 but not SRSF1 in hepatocytes have severe liver pathology and biochemical abnormalities. Histological analyses revealed generalized hepatitis with the presence of ballooned hepatocytes and evidence of fibrosis. Molecular analysis demonstrated that SRSF2 governs splicing of multiple genes involved in the stress-induced cell death pathway in the liver. More importantly, SRSF2 also functions as a potent transcription activator, required for efficient expression of transcription factors mainly responsible for energy homeostasis and bile acid metabolism in the liver. Consistent with the effects of SRSF2 in gene regulation, accumulation of total cholesterol and bile acids was prominently observed in the mutant liver, followed by enhanced generation of reactive oxygen species and increased endoplasmic reticulum stress, as revealed by biochemical and ultrastructural analyses. Taking these observations together, inactivation of SRSF2 in liver caused dysregulated splicing events and hepatic metabolic disorders, which trigger endoplasmic reticulum stress, oxidative stress, and finally liver failure.
刊物名称: MOLECULAR AND CELLULAR BIOLOGY
英文刊物名称: MOLECULAR AND CELLULAR BIOLOGY
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学科: Biochemistry & Molecular Biology; Cell Biology
英文学科: Biochemistry & Molecular Biology; Cell Biology
影响因子: 4.398
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论文类别: Article
英文论文类别: Article
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