Deletion of p38γ attenuates ethanol consumption- and acetaminophen-induced liver injury in mice through promoting Dlg1
| العنوان: | Deletion of p38γ attenuates ethanol consumption- and acetaminophen-induced liver injury in mice through promoting Dlg1 |
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| المؤلفون: | Jun Li, Hong Zhou, Yan Yao, Junfa Yang, Ying Hu, Shuang Hu, Tao Xu, Shu-xian Wang, Jing-Li Min, Chen-chen Yang, Ze-Yuan Wei, Yin-Cui Wu, Liang-yun Li |
| المصدر: | Acta Pharmacol Sin |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Liquid diet, medicine.disease_cause, Article, Mice, chemistry.chemical_compound, Internal medicine, medicine, Animals, Pharmacology (medical), Acetaminophen, Inflammation, Pharmacology, Liver injury, Ethanol, digestive, oral, and skin physiology, Fatty liver, General Medicine, medicine.disease, Mice, Inbred C57BL, Leukemia, Myeloid, Acute, Endocrinology, Liver, chemistry, Chemical and Drug Induced Liver Injury, Chronic, Chemical and Drug Induced Liver Injury, Steatosis, Steatohepatitis, Oxidative stress, medicine.drug |
| الوصف: | Acetaminophen (APAP) is one of the major causes of drug-induced acute liver injury, and ethanol may aggravate APAP-induced liver injury. The problem of ethanol- and APAP-induced liver injury becomes increasingly prominent, but the mechanism of ethanol- and APAP-induced liver injury remains ambiguous. p38γ is one of the four isoforms of P38 mitogen activated protein kinases, that contributes to inflammation in different diseases. In this study we investigated the role of p38γ in ethanol- and APAP-induced liver injury. Liver injury was induced in male C57BL/6 J mice by giving liquid diet containing 5% ethanol (v/v) for 10 days, followed by gavage of ethanol (25% (v/v), 6 g/kg) once or injecting APAP (200 mg/kg, ip), or combined the both treatments. We showed that ethanol significantly aggravated APAP-induced liver injury in C57BL/6 J mice. Moreover, the expression level of p38γ was up-regulated in the liver of ethanol-, APAP- and ethanol+APAP-treated mice. Knockdown of p38γ markedly attenuated liver injury, inflammation, and steatosis in ethanol+APAP-treated mice. Liver sections of p38γ-knockdown mice displayed lower levels of Oil Red O stained dots and small leaky shapes. AML-12 cells were exposed to APAP (5 mM), ethanol (100 mM) or combined treatments. We showed that P38γ was markedly increased in ethanol+APAP-treated AML-12 cells, whereas knockdown of p38γ significantly inhibited inflammation, lipid accumulation and oxidative stress in ethanol+APAP-treated AML-12 cells. Furthermore, we revealed that p38γ could combine with Dlg1, a member of membrane-associated guanylate kinase family. Deletion of p38γ up-regulated the expression level of Dlg1 in ethanol+APAP-treated AML-12 cells. In summary, our results suggest that p38γ functions as an important regulator in ethanol- and APAP-induced liver injury through modulation of Dlg1. [Image: see text] |
| تدمد: | 1745-7254 1671-4083 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52c33f0cecf5d43bab6c6d01ce7b92c8 https://doi.org/10.1038/s41401-021-00795-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....52c33f0cecf5d43bab6c6d01ce7b92c8 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17457254 16714083 |
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