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Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.

Publication ,  Journal Article
Choi, SS; Claridge, LC; Jhaveri, R; Swiderska-Syn, M; Clark, P; Suzuki, A; Pereira, TA; Mi, Z; Kuo, PC; Guy, CD; Pereira, FEL; Diehl, AM ...
Published in: Clin Sci (Lond)
June 2014

OPN (osteopontin)) is a Hh (Hedgehog)-regulated cytokine that is up-regulated during chronic liver injury and directly promotes fibrosis. We have reported that Hh signalling enhances viral permissiveness and replication in HCV (hepatitis C virus)-infected cells. Hence we hypothesized that OPN directly promotes HCV replication, and that targeting OPN could be beneficial in HCV. In the present study, we compared the expression of OPN mRNA and protein in HCV (JFH1)-infected Huh7 and Huh7.5 cells, and evaluated whether modulating OPN levels using exogenous OPN ligands (up-regulate OPN) or OPN-specific RNA-aptamers (neutralize OPN) leads to changes in HCV expression. Sera and livers from patients with chronic HCV were analysed to determine whether OPN levels were associated with disease severity or response to therapy. Compared with Huh7 cells, Huh7.5 cells support higher levels of HCV replication (15-fold) and expressed significantly more OPN mRNA (30-fold) and protein. Treating Huh7 cells with OPN ligands led to a dose-related increase in HCV (15-fold) and OPN (8-fold) mRNA. Conversely, treating Huh7.5 cells with OPN-specific RNA aptamers inhibited HCV RNA and protein by >50% and repressed OPN mRNA to basal levels. Liver OPN expression was significantly higher (3-fold) in patients with advanced fibrosis. Serum OPN positively correlated with fibrosis-stage (P=0.009), but negatively correlated with ETBCR (end-of-treatment biochemical response), ETVR (end-of-treatment virological response), SBCR (sustained biochemical response) and SVR (sustained virological response) (P=0.007). The OPN fibrosis score (serum OPN and presence of fibrosis ≥F2) may be a predictor of SVR. In conclusion, OPN is up-regulated in the liver and serum of patients with chronic hepatitis C, and supports increased viral replication. OPN neutralization may be a novel therapeutic strategy in chronic hepatitis C.

Duke Scholars

Published In

Clin Sci (Lond)

DOI

EISSN

1470-8736

Publication Date

June 2014

Volume

126

Issue

12

Start / End Page

845 / 855

Location

England

Related Subject Headings

  • Virus Replication
  • Up-Regulation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • Osteopontin
  • Middle Aged
  • Male
  • Humans
  • Hepatitis C, Chronic
  • Hepacivirus
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Choi, S. S., Claridge, L. C., Jhaveri, R., Swiderska-Syn, M., Clark, P., Suzuki, A., … Syn, W.-K. (2014). Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication. Clin Sci (Lond), 126(12), 845–855. https://doi.org/10.1042/CS20130473
Choi, Steve S., Lee C. Claridge, Ravi Jhaveri, Marzena Swiderska-Syn, Paul Clark, Ayako Suzuki, Thiago A. Pereira, et al. “Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.Clin Sci (Lond) 126, no. 12 (June 2014): 845–55. https://doi.org/10.1042/CS20130473.
Choi SS, Claridge LC, Jhaveri R, Swiderska-Syn M, Clark P, Suzuki A, et al. Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication. Clin Sci (Lond). 2014 Jun;126(12):845–55.
Choi, Steve S., et al. “Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.Clin Sci (Lond), vol. 126, no. 12, June 2014, pp. 845–55. Pubmed, doi:10.1042/CS20130473.
Choi SS, Claridge LC, Jhaveri R, Swiderska-Syn M, Clark P, Suzuki A, Pereira TA, Mi Z, Kuo PC, Guy CD, Pereira FEL, Diehl AM, Patel K, Syn W-K. Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication. Clin Sci (Lond). 2014 Jun;126(12):845–855.

Published In

Clin Sci (Lond)

DOI

EISSN

1470-8736

Publication Date

June 2014

Volume

126

Issue

12

Start / End Page

845 / 855

Location

England

Related Subject Headings

  • Virus Replication
  • Up-Regulation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • Osteopontin
  • Middle Aged
  • Male
  • Humans
  • Hepatitis C, Chronic
  • Hepacivirus