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JNK/MAPK pathway regulation by BEX2 gene silencing in alcoholic hepatitis mice: Effects on oxidative stress
Shuai Zhou1, Hai Zhong2, Yong Wang1
1Department of General Surgery, Anhui No. 2 Provincial People's Hospital, Anhui Medical University, Hefei, China.
Background:
Alcoholic hepatitis (AH) is a severe alcoholic-related liver disease that is a leading cause of morbidity and mortality, for which effective treatments are lacking. Brain-expressed X-linked gene 2 (BEX2) has been implicated in various diseases, but its association with AH has received limited attention. Thus, this study investigated BEX2's impact on the progression of AH by affecting the c-Jun NH2-terminal kinase/mitogen-activated protein kinase (JNK/MAPK) pathway.
Methods:
Microarray dataset GSE28619 from the Gene Expression Omnibus database was used to identify differentially expressed genes in AH. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), Western blot analysis, and flow cytometry were used to measure various factors in the liver tissue of AH mice.
Results:
BEX2 expression was significantly upregulated in the model. BEX2 gene silencing increased the levels of glutathione peroxidase and superoxide dismutase while decreasing malondialdehyde content; phosphorylation of JNK, c-JUN, and p38MAPK; apoptosis rate; and the extent of JNK/MAPK pathway activation.
Conclusions:
These findings provide valuable insights into the mechanisms underlying AH development and highlight the potential role of BEX2 gene expression as a promising therapeutic target for AH.
Insights
Brain-expressed X-linked gene 2 (BEX2) is upregulated in alcoholic hepatitis (AH). Silencing BEX2 reduces liver injury and inflammation, suggesting BEX2 as a potential therapeutic target for AH.
Area of Science:
- Hepatology
- Molecular Biology
- Gene Expression Analysis
Background:
- Alcoholic hepatitis (AH) is a severe liver disease with limited treatment options.
- Brain-expressed X-linked gene 2 (BEX2) role in AH is understudied.
- Investigating BEX2's involvement in AH pathogenesis is crucial.
Purpose of the Study:
- To explore the impact of BEX2 on alcoholic hepatitis progression.
- To elucidate the role of BEX2 in the c-Jun NH2-terminal kinase/mitogen-activated protein kinase (JNK/MAPK) pathway in AH.
Main Methods:
- Utilized Gene Expression Omnibus dataset GSE28619 for differential gene expression analysis in AH.
- Employed immunohistochemistry, TUNEL assay, Western blot, and flow cytometry in a mouse model of AH.
- Assessed BEX2 expression, oxidative stress markers, apoptosis, and JNK/MAPK pathway activation.
Main Results:
- BEX2 expression was significantly elevated in alcoholic hepatitis.
- BEX2 gene silencing improved antioxidant capacity (increased GPx, SOD; decreased MDA).
- BEX2 silencing reduced JNK/MAPK pathway activation, including p-JNK, p-c-JUN, and p-p38MAPK, and decreased apoptosis.
Conclusions:
- BEX2 upregulation is implicated in alcoholic hepatitis pathogenesis.
- Targeting BEX2 may offer a novel therapeutic strategy for alcoholic hepatitis.
- BEX2 influences AH progression via the JNK/MAPK signaling pathway.
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