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Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis.

Publication ,  Journal Article
Arffa, ML; Zapf, MA; Kothari, AN; Chang, V; Gupta, GN; Ding, X; Al-Gayyar, MM; Syn, W; Elsherbiny, NM; Kuo, PC; Mi, Z
Published in: PLoS One
2016

Osteopontin (OPN) promotes hepatic fibrosis, and developing therapies targeting OPN expression in settings of hepatic injury holds promise. The polyphenol epigallocatechin-3-gallate (EGCG), found in high concentrations in green tea, downregulates OPN expression through OPN mRNA degradation, but the mechanism is unknown. Previous work has shown that microRNAs can decrease OPN mRNA levels, and other studies have shown that EGCG modulates the expression of multiple microRNAs. In our study, we first demonstrated that OPN induces hepatic stellate cells to transform into an activated state. We then identified three microRNAs which target OPN mRNA: miR-181a, miR-10b, and miR-221. In vitro results show that EGCG upregulates all three microRNAs, and all three microRNAs are capable of down regulating OPN mRNA when administered alone. Interestingly, only miR-221 is necessary for EGCG-mediated OPN mRNA degradation and miR-221 inhibition reduces the effects of EGCG on cell function. In vivo experiments show that thioacetamide (TAA)-induced cell cytotoxicity upregulates OPN expression; treatment with EGCG blocks the effects of TAA. Furthermore, chronic treatment of EGCG in vivo upregulates all three microRNAs equally, suggesting that in more chronic treatment all three microRNAs are involved in modulating OPN expression. We conclude that in in vitro and in vivo models of TAA-induced hepatic fibrosis, EGCG inhibits OPN-dependent injury and fibrosis. EGCG works primarily by upregulating miR-221 to accelerate OPN degradation. EGCG may therefore have utility as a protective agent in settings of liver injury.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

12

Start / End Page

e0167435

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tea
  • Rats, Sprague-Dawley
  • Osteopontin
  • MicroRNAs
  • Male
  • Liver Cirrhosis
  • Humans
  • Hepatic Stellate Cells
  • Hep G2 Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Arffa, M. L., Zapf, M. A., Kothari, A. N., Chang, V., Gupta, G. N., Ding, X., … Mi, Z. (2016). Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis. PLoS One, 11(12), e0167435. https://doi.org/10.1371/journal.pone.0167435
Arffa, M. L., M. A. Zapf, A. N. Kothari, V. Chang, G. N. Gupta, X. Ding, M. M. Al-Gayyar, et al. “Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis.PLoS One 11, no. 12 (2016): e0167435. https://doi.org/10.1371/journal.pone.0167435.
Arffa ML, Zapf MA, Kothari AN, Chang V, Gupta GN, Ding X, et al. Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis. PLoS One. 2016;11(12):e0167435.
Arffa, M. L., et al. “Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis.PLoS One, vol. 11, no. 12, 2016, p. e0167435. Pubmed, doi:10.1371/journal.pone.0167435.
Arffa ML, Zapf MA, Kothari AN, Chang V, Gupta GN, Ding X, Al-Gayyar MM, Syn W, Elsherbiny NM, Kuo PC, Mi Z. Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis. PLoS One. 2016;11(12):e0167435.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2016

Volume

11

Issue

12

Start / End Page

e0167435

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tea
  • Rats, Sprague-Dawley
  • Osteopontin
  • MicroRNAs
  • Male
  • Liver Cirrhosis
  • Humans
  • Hepatic Stellate Cells
  • Hep G2 Cells