Cited by 315Iron Metabolism and DisordersCytokine Signaling Pathways and InteractionsTrace Elements in Health

The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.

STAT3 Is Required for IL-6-gp130–Dependent Activation of Hepcidin In Vivo

Open access

Abstract

Background & aims Hepcidin is a peptide hormone that is central to the regulation of iron homeostasis. In response to interleukin 6 (IL-6), hepatocytes produce hepcidin that decreases iron release/transfer from enterocytes and macrophages and causes hypoferremia. To clarify the molecular pathways involved in hepcidin activation by IL-6, we used different mice strains in which the main IL-6/gp130 signaling pathways have been genetically disrupted. Methods We generated mice with hepatocyte-specific deletion of the IL-6 signal-transducing gp130 receptor (alfpgp130 (LoxP/LoxP)), with a gp130 receptor lacking the essential region for STAT1 and -3 activation (alfpCre gp130(DeltaSTAT/LoxP)) or mice expressing a gp130 allele lacking the essential tyrosine for RAS-MAPK activation (alfpCregp130(Y757F/LoxP)). We studied gp130-dependent pathways and hepcidin mRNA expression by Western blot, reverse-transcription polymerase chain reaction, and Northern blot in vivo and ex vivo. Results IL-6 stimulated phospho STAT3, serum amyloid A (SAA), and suppressor of cytokine signaling 3 (SOCS3) expression in livers of wild-type and alfpCregp130(Y757F/LoxP) mice, whereas this response was blocked in alfpCre gp130(LoxP/LoxP) and alfpCre gp130(DeltaSTAT/LoxP) mice. In wild-type and alfpCregp130(Y757F/LoxP) animals, significantly higher hepcidin mRNA expression was found 3 to 6 hours after IL-6 stimulation. In contrast, no IL-6-dependent regulation of hepcidin mRNA expression was found in alfpgp130 (DeltaSTAT/LoxP) and AlfpCre gp130 (LoxP/LoxP) animals. In primary hepatocytes, higher hepcidin mRNA expression after IL-6 stimulation was only observed when gp130-STAT3-dependent signaling was intact. Conclusions We have demonstrated that both in vivo and in vitro STAT3 is the key transcription factor responsible for IL-6 activation of hepcidin gene expression in the liver.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1053/j.gastro.2006.10.018

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 43 references

1 of the 43 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Items 101–200 of 315

Metadata

Authors
Pietrangelo, A., Dierssen, U., Valli, L., Garuti, C., Rump, A., Corradini, E., Ernst, M., Klein, C., & Trautwein, C.
Affiliations
  • University of Modena and Reggio Emilia (IT)
  • Universitätsklinikum Aachen (DE)
  • Ludwig Cancer Research (BE)
Corresponding author
Trautwein, Christian
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2007-01
Volume
132
Issue
1
Pages
294-300
ISSN
0016-5085 (ISSN-L)
OpenAlex
W2046878952
Cited by
315
References
43
Citations by year
2026: 4 · 2025: 10 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 15 · 2020: 14 · 2019: 13 · 2018: 17 · 2017: 23 · 2016: 18 · 2015: 16 · 2014: 25 · 2013: 25 · 2012: 19
FWCI
11.19
Type
journal article
Language
en
Open access
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
hepcidin, STAT3, interleukin-6, gp130, iron homeostasis, hepatocytes, SOCS3, serum amyloid A, RAS/MAPK pathway, liver, hypoferremia, primary hepatocytes
MeSH terms
Suppressor of Cytokine Signaling 3 Protein, Animals, Iron, Mice, Mutant Strains, Phosphorylation, RNA, Messenger, Transcription, Genetic, Signal Transduction, Interleukin-6, Hepatocytes, Antimicrobial Cationic Peptides, STAT3 Transcription Factor, Cytokine Receptor gp130, Suppressor of Cytokine Signaling Proteins, Mice, Hepcidins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review