Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis

Sci Rep. 2017 Mar 6:7:43446. doi: 10.1038/srep43446.

Abstract

Although hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF), the mechanisms underlying liver fibrotic progression remain unclear. Here, we investigated the gene expression profiles of HBV-related LF patients. Whole genome expression arrays were used to detect gene expression in liver biopsy samples from chronically HBV infected patients. Through integrative data analysis, we identified several pathways and key genes involved in the initiation and exacerbation of liver fibrosis. Weight gene co-expression analysis revealed that integrin subunit β-like 1 (ITGBL1) was a key regulator of fibrogenesis. Functional experiments demonstrated that ITGBL1 was an upstream regulator of LF via interactions with transforming growth factor β1. In summary, we investigated the gene expression profiles of HBV-related LF patients and identified a key regulator ITGBL1. Our findings provide a foundation for future studies of gene functions and promote the development of novel antifibrotic therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Ontology
  • Hepatitis B Antibodies / genetics
  • Hepatitis B Antibodies / metabolism
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B e Antigens / genetics
  • Hepatitis B e Antigens / metabolism
  • Hepatitis B virus / pathogenicity
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / metabolism
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / virology
  • Host-Pathogen Interactions*
  • Humans
  • Integrin beta1 / genetics*
  • Integrin beta1 / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver / virology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Lymphokines / genetics
  • Lymphokines / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Annotation
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Biomarkers
  • DCDC2 protein, human
  • EHF protein, human
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • ITGBL1 protein, human
  • Integrin beta1
  • Lymphokines
  • Microtubule-Associated Proteins
  • PDGFD protein, human
  • Platelet-Derived Growth Factor
  • TGFB1 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta1