Premium
Helicobacter hepaticus infection induces chronic hepatitis and fibrosis in male BALB/c mice via the activation of NF‐κB, Stat3, and MAPK signaling pathways
Author(s) -
Cao Shuyang,
Zhu Chen,
Feng Jie,
Zhu Liqi,
Yin Jun,
Xu Yongliang,
Yang Haitao,
Huang Yuzheng,
Zhang Quan
Publication year - 2020
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/hel.12677
Subject(s) - biology , tumor necrosis factor alpha , inflammation , helicobacter , cirrhosis , immunology , medicine , helicobacter pylori , genetics
Background It has been documented that Helicobacter hepaticus ( H hepaticus ) infection is linked to chronic hepatitis and liver cancer. However, our understanding of the molecular mechanisms underlying progression of the H hepaticus‐ induced hepatic inflammation to cellular hepatocarcinoma is still limited. Materials and methods In our study, male BALB/c mice were infected by H hepaticus for 8, 12, 16, 20, and 24 weeks. Histopathology, H hepaticus colonization dynamics, select signaling pathways, and expression of key inflammatory cytokines in the liver were examined. Results We found that H hepaticus was detectible in feces of mice at 7 days postinfection (DPI) by PCR, but it was not detected in the livers by PCR until 8 weeks postinfection (WPI). In addition, abundance of colonic and hepatic H hepaticus was progressively increased over the infection duration. H hepaticus ‐induced hepatic inflammation and fibrosis were aggravated over the infection duration, and necrosis or cirrhosis developed in the infected liver at 24 WPI H hepaticus infection increased levels of alanine aminotransferase and aspartate aminotransferase. Moreover, mRNA levels of Il‐6 and Tnf‐α were significantly elevated in the livers of H hepaticus ‐infected mice compared to uninfected control from 8 WPI to 24 WPI. Furthermore, Stat3, nuclear factor‐κB (p65), and MAPK (Erk1/2 and p38) were activated by H hepaticus infection. Conclusions These data demonstrated that male BALB/c mice can be used as a new mouse model of H hepaticus ‐induced liver diseases and that the H hepaticus ‐induced liver injury is triggered by NF‐κB, Jak‐Stat, and MAPK signaling pathways.