LHBs can elevate the expression of MDR1 through HIF-1α in patients with CHB infection: a comparative proteomic study

Abstract

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.