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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Yang, Luo Liu, Xianzhi Zhen, Limin Liu, Ying Wu, Lina Xu, Wenxiong Peng, Liang Xie, Chan |
| Abstract | Background Hepatitis B virus (HBV) is an enveloped DNA virus that causes chronic hepatitis B (CHB) infection. Annexin, a Ca2+-activated protein, is widely expressed in various organs and tissues and has potential utility in disease diagnosis and treatment. However, the relationship between the annexin family and CHB remains unclear. Methods Clinical samples from hepatitis patients and donors or healthy individuals were collected. Transcriptome sequencing in CHB liver tissues and HBV-infected cells were performed. HepG2.2.15 cells with the full-length HBV genome and HBV-infected HepG2-NTCP cell models were established. HBV-infected mouse model was constructed and adeno-associated virus was utilized. Results ANXA4 expression was elevated during CHB infection. ANXA4 knockdown promoted HBV replication and aggravated liver injury, while ANXA4 overexpression alleviated that. Mechanistically, autophagy pathway was activated by ANXA4 deficiency, promoting autophagic degradation of minichromosome maintenance complex component 2 (MCM2). MCM2 inhibition activated HBV replication, while MCM2 overexpression attenuated ANXA4 deficiency-induced HBV replication and liver injury. Clinically, the expression of hepatitis B viral protein was negatively correlated with the ANXA4 levels, and CHB patients with high ANXA4 levels (> 8 ng/ml) showed higher sensitivity to interferon therapy. Conclusions ANXA4 functions as a protective factor during HBV infection. ANXA4 expression is elevated under HBV attack to restrict HBV replication by inhibiting autophagic degradation of MCM2, thereby alleviating liver injury and suppressing the CHB infection process. ANXA4 also enhances the sensitivity of CHB patients to interferon therapy. Therefore, ANXA4 is expected to be a new target for CHB treatment and prognostic evaluation. Graphical Abstract |
| Related Links | https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-024-03724-1.pdf |
| Ending Page | 20 |
| Page Count | 20 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17417015 |
| DOI | 10.1186/s12916-024-03724-1 |
| Journal | BMC Medicine |
| Issue Number | 1 |
| Volume Number | 22 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-11-07 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Biomedicine Chronic hepatitis B (CHB) Annexin A4 (ANXA4) Autophagy Minichromosome maintenance complex component 2 (MCM2) HBV replication Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 8.8/2023 |
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