eprintid: 13860
rev_number: 17
userid: 677
importid: 585
dir: disk0/00/01/38/60
datestamp: 2012-08-30 15:01:40
lastmod: 2019-02-02 13:58:17
status_changed: 2012-08-30 15:01:40
type: article
metadata_visibility: show
contact_email: wyang@ipb.pumc.edu.cn
item_issues_count: 0
eprint_status: archive
creators_name: Si, Y
creators_name: Liu, X
creators_name: Cheng, M
creators_name: Wang, M
creators_name: Gong, Q
creators_name: Yang, Y
creators_name: Wang, T
creators_name: Yang, W
contributors_type: http://www.loc.gov/loc.terms/relators/EDT
contributors_name: Jang, Sung Key
title: Growth differentiation factor 15 is induced by hepatitis C virus infection and regulates hepatocellular carcinoma-related genes
ispublished: pub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
abstract: Liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) are commonly induced by chronic hepatitis C virus (HCV) infection. We aimed to identify and characterize the involvement of previously screened cytokine GDF15 in HCV pathogenesis. We examined the GDF15 expression after HCV infection both in vitro and in vivo. Cultured JFH-1 HCV was used to determine the GDF15 function on virus propagation. GDF15 overexpression and RNA interference were employed to profile the GDF15-regulated genes, signaling pathways and cell biology phenotypes. The mRNA expression and protein secretion of GDF15 was dramatically increased in HCV-infected hepatoma cells, which maybe a host response to viral proteins or infection-induced cell stress. Patients infected with HCV had an average 15-fold higher blood GDF15 level than that of healthy volunteers. Three HCC individuals in the HCV cohort showed extremely high GDF15 concentrations. Transfection or exogenously supplied GDF15 enhanced HCV propagation, whereas knockdown of endogenous GDF15 resulted in inhibition of virus replication. Overexpressed GDF15 led to Akt activation and the phosphorylation of Akt downstream targeted GSK-3β and Raf. Several HCC-related molecules, such as E-cadherin, β-catenin, Cyclin A2/B1/D1, were up-regulated by GDF15 stimulation in vitro. Overexpression of GDF15 in hepatoma cells resulted in increased DNA synthesis, promoted cell proliferation, and importantly enhanced invasiveness of the cells. In conclusion, these results suggest that an elevated serum GDF15 level is a potential diagnostic marker for viral hepatitis, and GDF15 may contribute to HCV pathogenesis by altering the signaling and growth of host cells. © 2011 Si et al.
date: 2011-05-27
date_type: published
publication: PLoS ONE
volume: 6
number: 5
refereed: TRUE
id_number: 10.1371/journal.pone.0019967
other_id: NLM PMC3100307
pmcid: PMC3100307
pmid: 21625435
mesh_headings: Carcinoma, Hepatocellular--genetics
mesh_headings: Cell Line, Tumor
mesh_headings: Gene Expression Regulation, Neoplastic--physiology
mesh_headings: Growth Differentiation Factor 15--biosynthesis
mesh_headings: Hepatitis C--physiopathology
mesh_headings: Humans
mesh_headings: Liver Neoplasms--genetics
chemical_names: GDF15 protein, human
chemical_names: Growth Differentiation Factor 15
citation:   Si, Y and Liu, X and Cheng, M and Wang, M and Gong, Q and Yang, Y and Wang, T and Yang, W  (2011) Growth differentiation factor 15 is induced by hepatitis C virus infection and regulates hepatocellular carcinoma-related genes.  PLoS ONE, 6 (5).       
document_url: http://d-scholarship-dev.library.pitt.edu/13860/1/Growth_Differentiation_Factor_15.pdf
document_url: http://d-scholarship-dev.library.pitt.edu/13860/8/licence.txt