STAT3 cooperates with AR/CCRK signaling pathway in the progression of HBV infection and gender differences

• Published in: Journal of viral hepatitis
• Main Authors: Xu, Yanhui, Qi, Wenqian, Wang, Xu, Zhang, Yonggui, Han, Liang, Shi, Jingyi, Wang, Guohua, Liu, Jia, Duan, Honglei, Cong, Xianling, Zhao, Ping, Zhou, Changyu, Wang, Jiangbin
• Format: Journal Article
• Language: English
• Published: England 14.05.2022
• Subjects: chronic HBV infection; AR; CCRK; STAT3; gender differences
• ISSN: 1365-2893

The study aimed to investigate the role of AR/CCRK signaling pathway in chronic hepatitis B virus (HBV) infection and gender differences, and the contribution of AR regulatory factor STAT3 in it. AR, CCRK, and phosphorylated STAT3 expressions in liver tissues of chronic HBV-infected patients and non-HBV controls were determined by western blot and compared between genders. The relationships of expression levels with serum HBV DNA levels, liver inflammation activity and fibrosis score were analyzed in chronic HBV-infected patients. The relationships between expression levels of three proteins were also analyzed. HBV-infected patients had significantly higher expression levels of AR, CCRK, and p-STAT3 compared with controls (P<0.01). The expression levels of AR, CCRK, and p-STAT3 in chronic HBV-infected patients with severe inflammation were significantly higher than those with mild inflammation (P<0.05). Expression levels in patients with heavier fibrosis (stage F4) were higher than those with less fibrosis (stage F0-3) (P<0.01). No gender differences were observed in AR, CCRK and p-STAT3 levels in non-HBV controls; higher levels were observed in HBV-infected males than in HBV-infected females (P<0.05). AR, CCRK, and p-STAT3 levels in liver tissues positively correlated with each other (P<0.0001) and with serum HBV DNA levels (P<0.0001). In conclusion, in this study, we first found concordant over-expression of AR, CCRK and STAT3 in liver tissues of chronic HBV-infected patients who have not yet developed HCC, significantly correlated with the severity of the disease and showed gender differences. STAT3 may be a potential therapeutic co-target for chronic HBV infection.