Abstract
BackgroundHepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma. This study aims to enlighten pathways associated with HBV related liver fibrosis for delineation of potential new therapeutic targets and biomarkers.MethodsTissue samples from 47 HBV infected patients with different fibrotic stages (F1 to F6) were enrolled for 2D-DIGE proteomic screening. Differentially expressed proteins were identified by mass spectrometry and verified by western blotting. Functional proteomic associations were analyzed by EnrichNet application.ResultsFibrotic stage variations were observed for apolipoprotein A1 (APOA1), pyruvate kinase PKM (KPYM), glyceraldehyde 3-phospahate dehydrogenase (GAPDH), glutamate dehydrogenase (DHE3), aldehyde dehydrogenase (ALDH2), alcohol dehydrogenase (ALDH1A1), transferrin (TRFE), peroxiredoxin 3 (PRDX3), phenazine biosynthesis-like domain-containing protein (PBLD), immuglobulin kappa chain C region (IGKC), annexin A4 (ANXA4), keratin 5 (KRT5). Enrichment analysis with Reactome and Kegg databases highlighted the possible involvement of platelet release, glycolysis and HDL mediated lipid transport pathways. Moreover, string analysis revealed that HIF-1α (Hypoxia-inducible factor 1-alpha), one of the interacting partners of HBx (Hepatitis B X protein), may play a role in the altered glycolytic response and oxidative stress observed in liver fibrosis.ConclusionsTo our knowledge, this is the first protomic research that studies HBV infected fibrotic human liver tissues to investigate alterations in protein levels and affected pathways among different fibrotic stages. Observed changes in the glycolytic pathway caused by HBx presence and therefore its interactions with HIF-1α can be a target pathway for novel therapeutic purposes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-017-0114-4) contains supplementary material, which is available to authorized users.
Highlights
Hepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma
A recent study performed differential label-free proteomics approach using 27 biopsies from patients with HCV-associated hepatic fibrosis and reported alterations in lumican (LUM), fibulin 5 (FBLN5), cysteine and glycine-rich protein 2 (CSRP2), calponin 2 (CNN2), transgelin (TAGLN), collagen alpha-1(XIV) chain (COL14A1), and microfibril-associated protein 4 (MFAP-4), verify the expression of these proteins on a transcriptional level and with targeted proteomic approach in different cohorts composed by a total of 77 and 68 HBV or HCV infected patients with liver fibrosis, respectively [19]
These mentioned studies focuses on proteomics of HCV associated liver fibrosis, only the latter offered a partial targeted proteomic information about limited group corresponding to different fibrotic stages in HBV infection
Summary
Hepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma. A recent study performed differential label-free proteomics approach using 27 biopsies from patients with HCV-associated hepatic fibrosis and reported alterations in lumican (LUM), fibulin 5 (FBLN5), cysteine and glycine-rich protein 2 (CSRP2), calponin 2 (CNN2), transgelin (TAGLN), collagen alpha-1(XIV) chain (COL14A1), and MFAP-4, verify the expression of these proteins on a transcriptional level and with targeted proteomic approach in different cohorts composed by a total of 77 and 68 HBV or HCV infected patients with liver fibrosis, respectively [19]. A broad fibrotic stage specific proteomic profiling study of HBV associated liver fibrosis is still missing in literature
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