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Cited by 131Liver physiology and pathologyCytokine Signaling Pathways and InteractionsDrug-Induced Hepatotoxicity and Protection

Acute-phase response factor, increased binding, and target gene transcription during liver regeneration

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Trautwein, C, Rakemann, T, Niehof, M, Rose-John, S, Manns, MP·1996·Gastroenterology
DOI 10.1053/gast.1996.v110.pm8964411
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Abstract

Background & aims The acute-phase response may contribute and influence cell-cycle progression in hepatocytes. The aim of this study was to examine the regulation of the alpha 2-macroglobulin gene during liver regeneration and molecular mechanisms that influence its expression. Methods Partial hepatectomy or sham surgery was performed in Sprague-Dawley rats. At different time points after surgery blood was taken from the liver vein, and nuclear extracts and RNA were prepared. Northern blot analysis, run-off assays, gel shift experiments, and cytokine assays were performed. Results Increased transcription of the alpha 2-macroglobulin gene was found 12-24 hours posthepatectomy and not after sham surgery. Increased levels of alpha 2-macroglobulin messenger RNA correlated with enhanced binding of acute-phase response factor/signal transducer and activator of transcription 3 (APRF/Stat3) towards the cognate DNA sequence in the alpha 2-macroglobulin promoter and dramatically increased interleukin-6 levels in the liver vein. In contrast, nuclear translocation of APRF/Stat3 was detected as early as 1 hour after hepatectomy and up to 48 hours posthepatectomy. Therefore, two events can be distinguished in the regulation of APRF/Stat3: Its nuclear translocation and increased DNA binding. Conclusions Increased alpha 2-macroglobulin transcription posthepatectomy is achieved by increased levels of interleukin 6 and consecutive binding of APRF/Stat3 to the alpha 2-macroglobulin promoter. A two-step event is suggested for APRF/Stat3-dependent gene activation in hepatocytes.

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  • The levels of TNF and IL-6 increase after PH, with the peak of TNF circulating levels preceding the peak levels of IL-6.

    “The levels of these cytokines increase after PH, with the peak of TNF circulating levels preceding the peak levels of IL-6 (8,10,11).”

    From Expression of suppressors of cytokine signaling during liver regeneration (2001) · cites this paper as [10]

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Authors
Trautwein, C., Rakemann, T., Niehof, M., Rose-John, S., & Manns, M.
Affiliations
Medizinische Hochschule Hannover (DE)
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
1996-06
Volume
110
Issue
6
Pages
1854-1862
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/gast.1996.v110.pm8964411
OpenAlex
W2075848641
Cited by
131
References
8
Citations by year
2026: 3 · 2025: 2 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 1 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 4
FWCI
4.56
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
acute phase response, STAT3, alpha2-macroglobulin, liver regeneration, partial hepatectomy, interleukin-6, nuclear translocation, promoter binding, cytokine regulation of gene expression
MeSH terms
alpha-Macroglobulins, Animals, Base Sequence, Cell Nucleus, DNA-Binding Proteins, Hepatectomy, Liver Regeneration, Molecular Sequence Data, Postoperative Period, RNA, Messenger, Transcription Factors, Transcription, Genetic, Oligonucleotide Probes, Trans-Activators, Interleukin-6, Rats, Sprague-Dawley, STAT3 Transcription Factor, Rats

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