Next Article in Journal
Genetically Encoded Tools for Research of Cell Signaling and Metabolism under Brain Hypoxia
Previous Article in Journal
Natural Deep Eutectic Solvent as Extraction Media for the Main Phenolic Compounds from Olive Oil Processing Wastes
Open AccessArticle

Epigallocatechin-3-Gallate (EGCG)-Inducible SMILE Inhibits STAT3-Mediated Hepcidin Gene Expression

1
Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Korea
2
School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea
3
Department of Microbiology, Chonnam National University Medical School, Gwangju 61468, Korea
4
Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Seoul, 03722, Korea
5
Korea Basic Science Institute, Gwangju Center at Chonnam National University, Gwangju 61186, Korea
*
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(6), 514; https://doi.org/10.3390/antiox9060514
Received: 27 April 2020 / Revised: 27 May 2020 / Accepted: 9 June 2020 / Published: 11 June 2020
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
Hepatic peptide hormone hepcidin, a key regulator of iron metabolism, is induced by inflammatory cytokine interleukin-6 (IL-6) in the pathogenesis of anemia of inflammation or microbial infections. Small heterodimer partner-interacting leucine zipper protein (SMILE)/CREBZF is a transcriptional corepressor of nuclear receptors that control hepatic glucose and lipid metabolism. Here, we examined the role of SMILE in regulating iron metabolism by inflammatory signals. Overexpression of SMILE significantly decreased activation of the Janus kinase 2-signal transducer and activator of transcription 3 (STAT3)-mediated hepcidin production and secretion that is triggered by the IL-6 signal in human and mouse hepatocytes. Moreover, SMILE co-localized and physically interacted with STAT3 in the nucleus in the presence of IL-6, which significantly suppressed binding of STAT3 to the hepcidin gene promoter. Interestingly, epigallocatechin-3-gallate (EGCG), a major component of green tea, induced SMILE expression through forkhead box protein O1 (FoxO1), as demonstrated in FoxO1 knockout primary hepatocytes. In addition, EGCG inhibited IL-6-induced hepcidin expression, which was reversed by SMILE knockdown. Finally, EGCG significantly suppressed lipopolysaccharide-induced hepcidin secretion and hypoferremia through induction of SMILE expression in mice. These results reveal a previously unrecognized role of EGCG-inducible SMILE in the IL-6-dependent transcriptional regulation of iron metabolism. View Full-Text
Keywords: epigallocatechin-3-gallate; SMILE; IL-6; STAT3; FoxO1; hepcidin; iron metabolism; anemia of chronic disease epigallocatechin-3-gallate; SMILE; IL-6; STAT3; FoxO1; hepcidin; iron metabolism; anemia of chronic disease
Show Figures

Graphical abstract

MDPI and ACS Style

Kim, Y.-J.; Kim, K.-S.; Lim, D.; Yang, D.J.; Park, J.-I.; Kim, K.W.; Jeong, J.-H.; Choi, H.-S.; Kim, D.-K. Epigallocatechin-3-Gallate (EGCG)-Inducible SMILE Inhibits STAT3-Mediated Hepcidin Gene Expression. Antioxidants 2020, 9, 514.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop