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Helicobacter hepaticus infection induces chronic hepatitis and fibrosis in male BALB/c mice via the activation of NF-κB, Stat3, and MAPK signaling pathways.
- Source :
-
Helicobacter [Helicobacter] 2020 Apr; Vol. 25 (2), pp. e12677. Date of Electronic Publication: 2019 Dec 27. - Publication Year :
- 2020
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Abstract
- 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.<br />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.<br />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.<br />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.<br /> (© 2019 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Cytokines biosynthesis
Feces microbiology
Helicobacter Infections pathology
Liver microbiology
Liver pathology
Liver Neoplasms microbiology
Male
Mice
Mice, Inbred BALB C
Models, Animal
Signal Transduction
p38 Mitogen-Activated Protein Kinases metabolism
Fibrosis microbiology
Helicobacter hepaticus genetics
Helicobacter hepaticus isolation & purification
Hepatitis, Chronic microbiology
MAP Kinase Signaling System
NF-kappa B metabolism
STAT3 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1523-5378
- Volume :
- 25
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Helicobacter
- Publication Type :
- Academic Journal
- Accession number :
- 31881556
- Full Text :
- https://doi.org/10.1111/hel.12677