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Cited by 114Liver physiology and pathologyOrgan Transplantation Techniques and OutcomesWound Healing and Treatments

Global Changes in Interleukin–6-Dependent Gene Expression Patterns in Mouse Livers After Partial Hepatectomy

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Li, Wei, Liang, Xianping, Leu, Julie I., Kovalovich, Kellen, Ciliberto, Gennaro, Taub, Rebecca·2001·Hepatology
DOI 10.1053/jhep.2001.24431
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Abstract

Liver regeneration following 70% partial hepatectomy leads to rapid activation of genes in the remnant liver. Interleukin–6 deficient (IL–6 -/-) mice have impaired liver regeneration and abnormalities in immediate early gene expression. In this study, the gene expression program in the IL–6 +/+ and -/- livers at 2 hours posthepatectomy was examined with a cDNA array representing 588 highly regulated mouse genes. Thirty–six percent of the 103 immediate early genes were induced differently in IL–6 +/+ compared with IL–6 -/- livers, implying regulation by IL–6. IL–6 treatment of the IL–6 -/- mice in the absence of hepatectomy induced a much smaller set of genes in the liver, suggesting that IL–6 cooperates with other hepatectomy–induced factors to activate the large number of genes. Northern blot analyses were used to verify gene expression data obtained from the arrays. The expression of urokinase type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor–1 (PAI–1), critical components of the urokinase plasminogen activator (uPA) system, was lower and delayed in IL–6 -/- livers. Despite the fact that active uPAR/uPA complex is critical for hepatocyte growth factor (HGF) activation, no differences were detected between the IL–6 +/+ and -/- livers in HGF activation as measured by receptor phosphorylation. On the contrary, the mitogen–activated protein kinase (MAPK) pathway was activated in IL–6 +/+ livers early during regeneration but remarkably delayed in IL–6 -/- livers. Defective liver regeneration may be explained by the large number of gene activation pathways altered in IL–6 -/- livers and further supports the finding that IL–6 is necessary for normal liver regeneration.

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  • Three IL-6 target genes did not show IL-6 regulation posthepatectomy but were activated by IL-6 injection in the liver (TDAG51, membrane glycoprotein gp130, and Erp72).

    “Three did not show IL-6 regulation posthepatectomy but were activated by IL-6 injection in the liver (TDAG51, membrane glycoproteingp130, and Erp72, the endoplasmic reticulum stress protein) (4”

    From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [4]

    Table 1 (HEPATOLOGY June 2001 section; page not supplied) lists ERp72, gp130, and TDAG51 with differential expression between IL-6-positive and IL-6-deficient livers two hours after hepatectomy. That is contrary to the claim that these three showed no IL-6 regulation posthepatectomy. The table passage does not clearly establish the claimed injection result for all three. (LLM, conf=0.82)

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  • IL-6−/− mice have impaired liver regeneration characterized by liver necrosis and failure.

    “IL-6−/− mice have impaired liver regeneration characterized by liver necrosis and failure, a blunted DNA synthetic response in hepatocytes, and reduced gene activation during G1 phase.”

    From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [4]

    The introductory passage following the Abstract says IL-6-deficient mice have impaired regeneration and liver necrosis after 70% partial hepatectomy. It says they are prone to liver failure, rather than stating that liver failure occurs in all such mice; the claim omits that qualification. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • STAT3 is rapidly induced during liver regeneration in an IL-6-dependent fashion.

    “STAT3 is rapidly induced during liver regeneration in an interleukin 6 (IL-6)-dependent fashion, and IL-6 is required for normal liver regeneration.”

    From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [4]

  • IL-6 is required for normal liver regeneration.

    “STAT3 is rapidly induced during liver regeneration in an interleukin 6 (IL-6)-dependent fashion, and IL-6 is required for normal liver regeneration.”

    From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [4]

  • IL-6 is one of the most important initiators of the regenerative response.

    “Interleukin-6 (IL-6)1 is known as one of the most important initiators of the regenerative response (3”

    From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [4]

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Cited by

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Authors
Li, W., Liang, X., Leu, J. I., Kovalovich, K., Ciliberto, G., & Taub, R.
Affiliations
University of Pennsylvania (US)
Corresponding author
Taub, Rebecca
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2001-06
Volume
33
Issue
6
Pages
1377-1386
ISSN
0270-9139 (ISSN-L)
DOI
10.1053/jhep.2001.24431
OpenAlex
W2053451732
Cited by
114
References
4
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 9 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 6 · 2014: 5 · 2013: 2 · 2012: 3
FWCI
8.20
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 5205 d)
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Pennsylvania
  • National Institutes of Health (5r01dk049629-05)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-50306, DK-49629, P30DK050306)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
interleukin-6, liver regeneration, partial hepatectomy, gene expression, IL-6 knockout mice, immediate early genes, urokinase plasminogen activator system, uPAR, plasminogen activator inhibitor-1, hepatocyte growth factor, MAPK signaling, remnant liver
MeSH terms
Animals, Enzyme Activation, Hepatectomy, Liver, Liver Regeneration, Mice, Inbred C57BL, Postoperative Period, Reference Values, Time Factors, Interleukin-6, Gene Expression, Hepatocyte Growth Factor, Genes, Immediate-Early, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Mitogen-Activated Protein Kinases, Mice

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