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LHBs can elevate the expression of MDR1 through HIF-1α in patients with CHB infection: a comparative proteomic study
Shiying Li1, Yixuan Yang1, Xiangchun Ding2
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.
Insights
Hepatitis B virus (HBV) large surface protein (LHBs) and HIF-1α may drive multi-drug resistance protein 1 (MDR1) overexpression in chronic hepatitis B (CHB) infection, contributing to liver disease progression.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatitis B virus (HBV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC).
- Understanding the molecular mechanisms underlying HBV pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To identify differentially expressed proteins (DEPs) in liver tissues of patients with chronic hepatitis B (CHB).
- To elucidate the role of specific proteins and transcription factors in HBV-related liver disease.
Main Methods:
- Proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometry on liver samples from CHB patients and controls.
- Validation of protein expression using RT-qPCR and western blot.
- Electrophoretic mobility shift assay (EMSA) and reporter gene assays to confirm transcription factor function.
Main Results:
- Seventy-one differentially expressed proteins (DEPs) were identified in CHB liver tissues.
- Overexpression of multi-drug resistance protein 1 (MDR1) was confirmed at both mRNA and protein levels.
- HBV large surface protein (LHBs) increased MDR1 expression, potentially mediated by hypoxia-inducible factor 1α (HIF-1α).
Conclusions:
- HBV LHBs, in conjunction with HIF-1α, induces MDR1 overexpression.
- MDR1 upregulation may play a role in the pathological changes observed in chronic hepatitis B infection.
Background And Aims:
Hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). To gain a better understanding of the pathogenesis of HBV infection, this study aimed to investigate the differentially expressed proteins (DEPs) in liver tissues from patients with chronic hepatitis B (CHB) infection.
Results:
Seventy-one DEPs were identified. Overexpression of multi-drug resistance protein 1 (MDR1) was validated by RT-qPCR and western blot analyses. Moreover, its expression was increased at both the mRNA and protein levels in response to overexpression of HBV large surface protein (LHBs). Furthermore, screening of transcription factors suggested the possible involvement of hypoxia-inducible factor 1α (HIF-1α) in the interaction between LHBs and MDR1. The function of HIF-1α in the MDR1 activation was confirmed by EMSA and reporter gene analyses.
Materials And Methods:
Liver samples from CHB patients and controls without HBV infection were collected and subjected to isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometric analysis.
Conclusions:
These results imply that LHBs, in association with HIF-1α, induces MDR1 overexpression, which may contribute to the pathogenic changes in CHB infection.
