Upregulation of Nrf2 Expression in Non-Alcoholic Fatty Liver and Steatohepatitis

Xu, Weihua; Shao, Luolin; Zhou, Cheng-Jun; Wang, Hongbo; Guo, Jianqiang

doi:10.5754/hge10501

Cited by 23 publications

(26 citation statements)

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“…Many researches have demonstrated that Nrf2 prevents the liver from many hepatotoxicants. The Nrf2-mediated protection is accompanied by induction of antioxidant genes, suppression of inflammatory responses, inhibition of apoptosis and attenuation of oxidative stress [7,8,10].…”

Section: Introductionmentioning

confidence: 99%

“…Nuclear factor E2-related factor 2 (Nrf2) is referred to as the ''master regulator'' of the antioxidant response via the antioxidant response elements (ARE), modulating the expression of hundreds of genes, including not only the familiar antioxidant enzymes, but large numbers of genes that control seemingly disparate processes such as immune and inflammatory responses, tissue remodelling and fibrosis, carcinogenesis and metastasis, and even cognitive dysfunction and addictive behavior [7][8][9]. Many researches have demonstrated that Nrf2 prevents the liver from many hepatotoxicants.…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway

Ding

Zhang

et al. 2015

Clinics and Research in Hepatology and Gastroenterology

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway

Ding

Zhang

et al. 2015

Clinics and Research in Hepatology and Gastroenterology

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“…Nuclear factor erythroid-2-related factor 2 (Nrf2) is known as the “primary supervisor” of the antioxidant response through the antioxidant response elements (AREs), regulating the expression of numerous genes including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutathione S -transferase (GST) and several adenosine triphosphate-dependent drug efflux pumps (multidrug resistance proteins) 3–5. Therefore, many studies have demonstrated that Nrf2 is a transcription factor that can regulate various cytoprotective genes.…”

Section: Introductionmentioning

confidence: 99%

Ursolic acid sensitizes cisplatin-resistant HepG2/DDP cells to cisplatin via inhibiting Nrf2/ARE pathway

Wu¹,

Zhang

Du³

2016

DDDT

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BackgroundCombinations of adjuvant sensitizers with anticancer drugs is a promising new strategy to reverse chemoresistance. Ursolic acid (UA) is one of the natural pentacyclic triterpene compounds known to have many pharmacological characteristics such as anti-inflammatory and anticancer properties. This study investigates whether UA can sensitize hepatocellular carcinoma cells to cisplatin.Materials and methodsCells were transfected with nuclear factor erythroid-2-related factor 2 (Nrf2) small interfering RNA and Nrf2 complementary DNA by using Lipofectin 2000. The cytotoxicity of cells was investigated by Cell Counting Kit 8 assay. Cell apoptosis, cell cycle, reactive oxygen species, and mitochondrial membrane potential were detected by flow cytometry fluorescence-activated cell sorting. The protein level of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and heme oxygenase-1 (HO-1) was detected by Western blot analysis.ResultsThe results showed that the reverse index was 2.9- and 9.69-fold by UA of 1.125 μg/mL and 2.25 μg/mL, respectively, for cisplatin to HepG2/DDP cells. UA–cisplatin combination induced cell apoptosis and reactive oxygen species, blocked the cell cycle in G0/G1 phase, and reduced the mitochondrial membrane potential. Mechanistically, UA–cisplatin dramatically decreased the expression of Nrf2 and its downstream genes. The sensibilization of UA–cisplatin combination was diminished in Nrf2 small interfering RNA-transfected HepG2/DDP cells, as well as in Nrf2 complementary DNA-transfected HepG2/DDP cells.ConclusionThe results confirmed the sensibilization of UA on HepG2/DDP cells to cisplatin, which was possibly mediated via the Nrf2/antioxidant response element pathway.

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“…Free Nrf2, dissociated from keap1, moves into the nucleus, combines with ARE, and serves as a transcriptional factor to regulate the expression of corresponding downstream genes ( e.g ., GSH and HO-1 ). This comes with enhanced oxidation resistance and reduced oxidative stress[6,7,26]. So, the means by which to increase the expression of Nrf2 or promote Nrf2 nuclear translocation could be an important target for the treatment and prevention of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant axis Nrf2-keap1-ARE in inhibition of alcoholic liver fibrosis by IL-22

2017

WJG

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AIMTo explore the effect of interleukin (IL)-22 on in vitro model of alcoholic liver fibrosis hepatic stellate cells (HSCs), and whether this is related to regulation of Nrf2-keap1-ARE.METHODSHSC-T6 cells were incubated with 25, 50, 100, 200 and 400 μmol/L acetaldehyde. After 24 and 48 h, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect proliferation of HSCs to choose the best concentration and action time. We used the optimal concentration of acetaldehyde (200 μmol/L) to stimulate HSCs for 24 h, and treated the cells with a final concentration of 10, 20 or 50 ng/mL IL-22. The cell proliferation rate was detected by MTT assay. The cell cycle was analyzed by flow cytometry. The expression of nuclear factor-related factor (Nrf)2 and α-smooth muscle antigen was detected by western blotting and immunocytochemistry. The levels of malondialdehyde (MDA) and glutathione (GSH) were measured by spectrophotometry.RESULTSIn the MTT assay, when HSCs were incubated with acetaldehyde, activity and proliferation were higher than in the control group, and were most obvious after 48 h treatment with 200 μmol/L acetaldehyde. The number of cells in G0/G1 phases was decreased and the number in S phase was increased in comparison with the control group. When treated with different concentrations of IL-22, HSC-T6 cell activity and proliferation rate were markedly decreased in a dose-dependent manner, and cell cycle progression was arrested from G1 to S phase. Western blotting and immunocytochemistry demonstrated that expression of Nrf2 total protein was not significantly affected. Expression of Nrf2 nuclear protein was low in the control group, increased slightly in the model group (or acetaldehyde-stimulated group), and increased more obviously in the IL-22 intervention groups. The levels of MDA and GSH in the model group were significantly enhanced in comparison with those in the control group. In cells treated with IL-22, the MDA level was attenuated but the GSH level was further increased. These changes were dose-dependent.CONCLUSIONIL-22 inhibits acetaldehyde-induced HSC activation and proliferation, which may be related to nuclear translocation of Nrf2 and increased activity of the antioxidant axis Nrf2-keap1-ARE.

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Upregulation of Nrf2 Expression in Non-Alcoholic Fatty Liver and Steatohepatitis

Cited by 23 publications

References 0 publications

Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway

Protective effects of ursolic acid in an experimental model of liver fibrosis through Nrf2/ARE pathway

Ursolic acid sensitizes cisplatin-resistant HepG2/DDP cells to cisplatin via inhibiting Nrf2/ARE pathway

Antioxidant axis Nrf2-keap1-ARE in inhibition of alcoholic liver fibrosis by IL-22

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