The role of human cytochrome P450 2E1 in liver inflammation and fibrosis
| العنوان: | The role of human cytochrome P450 2E1 in liver inflammation and fibrosis |
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| المؤلفون: | Hsiao-Yen Ma, Jun Xu, David A. Brenner, Ronglin Hu, Edward A. Dennis, Shuang Liang, Tatiana Kisseleva, Yukinori Koyama, Mengxi Sun, Oswald Quehenberger, Gabriel Karin, Nicholas O. Davidson |
| المصدر: | Hepatology Communications Hepatology communications, vol 1, iss 10 |
| بيانات النشر: | John Wiley and Sons Inc., 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Alcoholic liver disease, Chronic Liver Disease and Cirrhosis, Biology, medicine.disease_cause, Oral and gastrointestinal, Proinflammatory cytokine, Alcohol Use and Health, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, 2.1 Biological and endogenous factors, Hepatology, Liver Disease, Substance Abuse, Original Articles, CYP2E1, medicine.disease, Hepatic stellate cell activation, 3. Good health, Alcoholism, 030104 developmental biology, Endocrinology, Hepatic stellate cell, 030211 gastroenterology & hepatology, Original Article, Steatosis, Digestive Diseases, Oxidative stress |
| الوصف: | Cytochrome P450 2E1 (CYP2E1) plays an important role in alcohol and toxin metabolism by catalyzing the conversion of substrates into more polar metabolites and producing reactive oxygen species. Reactive oxygen species-induced oxidative stress promotes hepatocyte injury and death, which in turn induces inflammation, activation of hepatic stellate cells, and liver fibrosis. Here, we analyzed mice expressing only the human CYP2E1 gene (hCYP2E1) to determine differences in hCYP2E1 versus endogenous mouse Cyp2e1 function with different liver injuries. After intragastric alcohol feeding, CYP2E1 expression was induced in both hCYP2E1 and wild-type (Wt) mice. hCYP2E1 mice had greater inflammation, fibrosis, and lipid peroxidation but less hepatic steatosis. In addition, hCYP2E1 mice demonstrated increased expression of fibrogenic and proinflammatory genes but decreased expression of de novo lipogenic genes compared to Wt mice. Lipidomics of free fatty acid, triacylglycerol, diacylglycerol, and cholesterol ester species and proinflammatory prostaglandins support these conclusions. Carbon tetrachloride-induced injury suppressed expression of both mouse and human CYP2E1, but again hCYP2E1 mice exhibited greater hepatic stellate cell activation and fibrosis than Wt controls with comparable expression of proinflammatory genes. By contrast, 14-day bile duct ligation induced comparable cholestatic injury and fibrosis in both genotypes. Conclusion: Alcohol-induced liver fibrosis but not hepatic steatosis is more severe in the hCYP2E1 mouse than in the Wt mouse, demonstrating the use of this model to provide insight into the pathogenesis of alcoholic liver disease. (Hepatology Communications 2017;1:1043-1057). |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2471-254X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac69fa119595b165fe539dba3f76e6ee http://europepmc.org/articles/PMC5721400 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ac69fa119595b165fe539dba3f76e6ee |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2471254X |
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