Hepcidin inhibits Smad3 phosphorylation in hepatic stellate cells by impeding ferroportin-mediated regulation of Akt

Chang Yeob Han, Ja Hyun Koo, Sung Hoon Kim, Sara Gardenghi, Stefano Rivella, Pavel Strnad, Se Jin Hwang and Sang Geon Kim ()
Additional contact information
Chang Yeob Han: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University
Ja Hyun Koo: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University
Sung Hoon Kim: College of Medicine, Hanyang University
Sara Gardenghi: Weill Cornell Medical College
Stefano Rivella: Weill Cornell Medical College
Pavel Strnad: University Hospital Aachen
Se Jin Hwang: College of Medicine, Hanyang University
Sang Geon Kim: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Hepatic stellate cell (HSC) activation on liver injury facilitates fibrosis. Hepatokines affecting HSCs are largely unknown. Here we show that hepcidin inhibits HSC activation and ameliorates liver fibrosis. We observe that hepcidin levels are inversely correlated with exacerbation of fibrosis in patients, and also confirm the relationship in animal models. Adenoviral delivery of hepcidin to mice attenuates liver fibrosis induced by CCl4 treatment or bile duct ligation. In cell-based assays, either hepcidin from hepatocytes or exogenous hepcidin suppresses HSC activation by inhibiting TGFβ1-mediated Smad3 phosphorylation via Akt. In activated HSCs, ferroportin is upregulated, which can be prevented by hepcidin treatment. Similarly, ferroportin knockdown in HSCs prohibits TGFβ1-inducible Smad3 phosphorylation and increases Akt phosphorylation, whereas ferroportin over-expression has the opposite effect. HSC-specific ferroportin deletion also ameliorates liver fibrosis. In summary, hepcidin suppresses liver fibrosis by impeding TGFβ1-induced Smad3 phosphorylation in HSCs, which depends on Akt activated by a deficiency of ferroportin.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms13817 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13817

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13817

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().