title: LHBs can elevate the expression of MDR1 through HIF-1α in patients with CHB infection: a comparative proteomic study.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Key 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.
authors.forename: Shiying
authors.initials: S
authors.lastname: Li
authors.affiliation: Key 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.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, PR China.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Ding
authors.affiliation: Key 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.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key 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.
authors.forename: Sha
authors.initials: S
authors.lastname: She
authors.affiliation: Key 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Peng
authors.affiliation: Key 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.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key 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.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ran
authors.affiliation: Key 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.
authors.forename: Sanglin
authors.initials: S
authors.lastname: Li
authors.affiliation: Key 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Key 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.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Key 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.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000378:metabolism / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D014759:Viral Envelope Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins
keywords: HIF-1α; LHBs; MDR1; iTRAQ; proteomics