The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.
Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration
Open accessAbstract
Background & aims Liver regeneration after loss of hepatic tissue leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Interleukin (IL)-6 is a key inducer of transcription factors involved in liver regeneration. Whenever IL-6 activates target cells, it binds to a specific IL-6 receptor (IL-6R). The IL-6/IL-6R complex then associates with the signal transducer gp130, leading to activation of intracellular signaling. Methods We have recently constructed the designer cytokine Hyper-IL-6 consisting of soluble IL-6R covalently linked to IL-6, which directly stimulates gp130 even in the absence of membrane-bound IL-6R. We compared the influence of IL-6 and Hyper-IL-6 on liver regeneration after partial hepatectomy in mice. Results The IL-6/soluble IL-6 fusion protein Hyper-IL-6, but not IL-6 alone, led to an earlier onset of hepatocellular proliferation resulting in an acceleration of liver weight restoration. Also, during liver regeneration, soluble IL-6R levels were increased. Conclusions These results emphasize a central role for IL-6 and soluble IL-6R in liver regeneration and indicate a possible therapeutic potential for the designer cytokine Hyper-IL-6 in clinical situations associated with liver regeneration such as acute hepatic failure or resection of chronically damaged liver tissue.
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“Although the classic or cis-signaling of IL-6 is determined to promote the compensatory proliferation of hepatocytes, its trans-signaling in liver regeneration is more important [19, 25–27].”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [25]
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“IL-6 classic and trans-signaling on hepatocytes expressing IL-6R induce STAT3 phosphorylation and accelerate liver regeneration (Peters et al., 2000”
From Targeting Interleukin-6 Signaling in Clinic (2019) · cites this paper as Peters et al., 2000
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Cites
Experimental pathology of the liver
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Higgins, G. (1931) · Cited by 2,444
Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice
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gp 130 AND THE INTERLEUKIN-6 FAMILY OF CYTOKINES
Taga, T., & Kishimoto, T. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.797 · Cited by 1,468
Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
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Cloning and Expression of the Human Interleukin-6 (BSF-2/IFNβ 2) Receptor
Yamasaki, K., Taga, T., Hirata, Y., Yawata, H., Kawanishi, Y., Seed, B., Taniguchi, T., Hirano, T., & Kishimoto, T. (1988) · Science · doi:10.1126/science.3136546 · Cited by 1,059
Molecular cloning and expression of an IL-6 signal transducer, gp130
Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T., & Kishimoto, T. (1990) · Cell · doi:10.1016/0092-8674(90)90411-7 · Cited by 1,039
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Cited by
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The pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212
Self-citationLiver regeneration: from myth to mechanism
Taub, R. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1489 · Cited by 1,567
IL-6 pathway in the liver: From physiopathology to therapy
Schmidt-Arras, D., & Rose-John, S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.004 · Cited by 881
Self-citationTargeting Interleukin-6 Signaling in Clinic
Kang, S., Tanaka, T., Narazaki, M., & Kishimoto, T. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.026 · Cited by 904
Interleukin-6 Family CytokinesPreprint
Rose‐John, S. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028415 · Cited by 846
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Metadata
- Authors
- Peters, M., Blinn, G., Jostock, T., Schirmacher, P., Büschenfelde, K. M. Z., Galle, P. R., & Rose–John, S.
- Affiliations
- University of Cologne (DE)
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 119
- Issue
- 6
- Pages
- 1663-1671
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W1989052869
- Cited by
- 129
- References
- 36
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 12 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 5
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- interleukin-6, soluble IL-6 receptor, liver regeneration, partial hepatectomy, hyper-IL-6, gp130 signaling, hepatocyte proliferation, acute liver failure, cytokine fusion proteins
- MeSH terms
- Animals, Cell Division, DNA-Binding Proteins, Gene Expression Regulation, Hepatectomy, Humans, Liver, Liver Regeneration, Mice, Inbred C57BL, Organ Size, Phosphorylation, Postoperative Period, Solubility, Time Factors, Trans-Activators, Interleukin-6, Receptors, Interleukin-6, STAT3 Transcription Factor, Mice
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