Mangiferin alleviates endoplasmic reticulum stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis
Autor: | Shuanghong Jin, Ping Chen, Guangyao Zhou, Lingxiang Jin, Shaoxun Li, Jie Li, Yiping Chen, Chenwei Pan, Weilai Chen, Peipei Fang, Jiake Yu |
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Rok vydání: | 2020 |
Předmět: |
Lipopolysaccharides
Male Untranslated region NF-E2-Related Factor 2 Xanthones Apoptosis medicine.disease_cause environment and public health Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Luciferase Mangiferin Molecular Biology Cells Cultured 030304 developmental biology 0303 health sciences Gene knockdown Endoplasmic reticulum General Medicine respiratory system Endoplasmic Reticulum Stress Cell biology Disease Models Animal MicroRNAs Oxidative Stress chemistry 030220 oncology & carcinogenesis Unfolded protein response Liver function Chemical and Drug Induced Liver Injury Oxidative stress Signal Transduction |
Zdroj: | The Journal of Biochemistry. 168:365-374 |
ISSN: | 1756-2651 0021-924X |
DOI: | 10.1093/jb/mvaa056 |
Popis: | This study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3′-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis. |
Databáze: | OpenAIRE |
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