Inflammation regulates TMPRSS6 expression via STAT5

Meynard, Delphine, Sun, Chia Chi, Wu, Qifang, Chen, Wenjie, Chen, Shanzhuo, Nelson, Caroline N., Waters, Michael J., Babitt, Jodie L. and Lin, Herbert Y. (2013) Inflammation regulates TMPRSS6 expression via STAT5. PLoS One, 8 12: e82127.1-e82127.10. doi:10.1371/journal.pone.0082127

Author Meynard, Delphine
Sun, Chia Chi
Wu, Qifang
Chen, Wenjie
Chen, Shanzhuo
Nelson, Caroline N.
Waters, Michael J.
Babitt, Jodie L.
Lin, Herbert Y.
Title Inflammation regulates TMPRSS6 expression via STAT5
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0082127
Open Access Status DOI
Volume 8
Issue 12
Start page e82127.1
End page e82127.10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
TMPRSS6 is a regulated gene, with a crucial role in the regulation of iron homeostasis by inhibiting hepcidin expression. The main regulator of iron homeostasis, the antimicrobial peptide hepcidin, which also has a role in immunity, is directly upregulated by inflammation. In this study, we analyzed whether inflammation is also a modulator of TMPRSS6 expression in vitro and in vivo and we determined the mechanism of this regulation A Human Hepatoma cell line was treated with interleukin-6 and mice were injected with lipopolysaccharide and TMPRSS6 expression and the regulatory mechanism were addressed. In this study, we demonstrate that inflammation downregulates TMPRSS6 expression in vitro and in vivo. The downregulation of Tmprss6 by inflammation in mice is not dependent on the Bmp-Smad pathway but occurs through a decrease in Stat5 phosphorylation. Moreover, Stat5 positively regulates Tmprss6 expression directly by binding to a Stat5 element located on the Tmprss6 promoter. Importantly, our results highlight the functional role of inflammatory modulation of TMPRSS6 expression in the regulation of hepcidin. TMPRSS6 inhibition via decreased STAT5 phosphorylation may be an additional mechanism by which inflammation stimulates hepcidin expression to regulate iron homeostasis and immunity.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID RO1 DK087727
RO1 DK-069533
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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