JNK /MAPK pathway regulation by BEX2 gene silencing in alcoholic hepatitis mice: Effects on oxidative stress
Shuai Zhou, Hai Zhong, Yong Wang, Xiaoguang Wang, Hongtao Pan, Xiaolin Liu, Lingyu Hu Abstract
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. Therefore, this study aimed to investigate BEX2's ability to impact 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
Our results indicate that BEX2 expression was significantly upregulated in the model. BEX2 gene silencing increased the levels of glutathione peroxidase (GPX) and superoxide dismutase (SOD) while decreasing the malondialdehyde (MDA) content, phosphorylation of JNK, c‐JUN, and p38MAPK, apoptosis rate, and the extent of JNK/MAPK pathway activation, highlighting its potential role as a promising therapeutic target for AH.
Conclusions
These findings provide valuable insights into the mechanisms underlying AH development and the development of effective treatments for this deadly disease.