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.
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.
Integrity signals
Registry
Cites
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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
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
Experimental pathology of the liver
Higgins, G. (1931) · Medical Entomology and Zoology · Cited by 4,057
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828
Gratzner, H. G. (1982) · Science · doi:10.1126/science.7123245 · Cited by 2,653
Higgins, G. (1931) · Cited by 2,444
Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice
Cressman, D. E., Greenbaum, L. E., DeAngelis, R. A., Ciliberto, G., Furth, E. E., Poli, V., & Taub, R. (1996) · Science · doi:10.1126/science.274.5291.1379 · Cited by 1,538
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
Taga, T., Hibi, M., Hirata, Y., Yamasaki, K., Yasukawa, K., Matsuda, T., Hirano, T., & Kishimoto, T. (1989) · Cell · doi:10.1016/0092-8674(89)90438-8 · Cited by 1,396
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
Yamada, Y., Kirillova, I., Peschon, J. J., & Fausto, N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1441 · Cited by 944
Flagged first, then by citations
1 of the 36 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–129 of 129
Chai, S., Guo, S., Yang, J., Lu, S., Yuan, Y., Li, H., Sun, P., Zhang, T., Xu, B., Sun, H., et al. (2021) · Europe PMC (PubMed Central) · Cited by 7
Zhu, Y., Li, Z., Zhang, J., Liu, M., Jiang, X., & Li, B. (2022) · BMC Genomics · doi:10.1186/s12864-022-08891-0 · Cited by 7
Wang, C.-H., Chen, C.-Y., Wang, K., Kao, A., Chen, Y.-J., Lin, P.-H., Chen, M. J., Wu, T.-Y., Cheng, J., Lee, K., et al. (2023) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szac084 · Cited by 7
Molecular Pathways Governing the Termination of Liver Regeneration
de Haan, L. R., van Golen, R. F., & Heger, M. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.000955 · Cited by 10
Ito, Y., Eguchi, S., Kamohara, Y., Inuo, H., Yamanouchi, K., Okudaira, S., Yanaga, K. K., Furui, J., & Kanematsu, T. (2004) · The International Journal of Artificial Organs · doi:10.1177/039139880402700406 · Cited by 7
Ariki, N., Morimoto, Y., Yagi, T., Oyama, T., Cyouda, Y., Sadamori, H., Inagaki, M., Urushihara, N., Iwagaki, H., & Tanaka, N. (2003) · Journal of International Medical Research · doi:10.1177/147323000303100302 · Cited by 7
Rose‐John, S. (2006) · Handbook of experimental pharmacology · doi:10.1007/3-540-31265-x_10 · Cited by 7
Self-citationRatti, F., Pulitanò, C., Catena, M., Paganelli, M., & Aldrighetti, L. A. (2015) · Hepatology Research · doi:10.1111/hepr.12585 · Cited by 5
Immunology and treatments of fatty liver disease
Tang, S., Wu, S., Zhang, W., Ma, L., Zuo, L., & Wang, H. (2024) · Archives of Toxicology · doi:10.1007/s00204-024-03920-1 · Cited by 6
Cytokine Engineering Approaches for Regenerative Medicine
Li, S., You, W., & Martino, M. M. (2025) · Advanced Therapeutics · doi:10.1002/adtp.202500103 · Cited by 5
Increased levels of systemic iron content in adult-onset interleukin-6 knockout mice
Zhang, F., Zhang, C., Luo, Q., Li, J., Qiu, X., & Qian, Z. (2025) · Redox Report · doi:10.1080/13510002.2025.2602306 · Cited by 1
Refining therapeutic targeting of interleukin-6 by signalling mode selectivity
Rose‐John, S., Waetzig, G. H., & Schreiber, S. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-026-01536-x · Cited by 1
Self-citationStem cell signaling molecules and pathways in liver regeneration
Chawla, S., & Das, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18800-8.00014-9 · Cited by 1
Papel de la caveolina en proliferación y en regeneración hepática
Moñibas, R. M., & Gomar, L. B. (2011) · Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya) · doi:10.13140/2.1.3048.1443 · Cited by 1
Taub, R. A. (2005) · Springer eBooks · doi:10.1007/3-540-27194-5_7 · Cited by 1
Dong, J., Viswanathan, S., Adami, E., Schäfer, S., Kuthubudeen, F. F., Widjaja, A. A., & Cook, S. A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.05.438446 · Cited by 1
Bösch, R. V. (2010) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.10.2010.tde-03082010-120238
6. GROWTH FACTORS AND THE LIVER
Selden, C. (2004) · Principles of medical biology · doi:10.1016/s1569-2582(04)15006-x
Señales que regulan la expresión de genes en la regeneración hepática
Angosto, M. C. (2009) · Dialnet (Universidad de la Rioja)
Inderbitzin, D., Sidler, D., Avital, I., & Candinas, D. (2006) · Journal of Organ Dysfunction · doi:10.1080/17471060600986143
Original article: ERYTHROPOIETIN STIMULATES HEPATOCYTE REGENERATION AFTER LIVER RESECTION
Schön, M. P., Hogrebe, E., Hengstler, J. G., Donaubauer, B., Faber, S. C., Bauer, A., Pietsch, U., JELKMANN, W. E. B., Thiery, J., Hauss, J., et al. (2008)
Dancygier, H. (2009) · Springer eBooks · doi:10.1007/978-3-540-93842-2_13
(2007) · The Egyptian Journal of Hospital Medicine · doi:10.21608/ejhm.2007.17702
Dancygier, H. (2003) · Springer eBooks · doi:10.1007/978-3-642-55902-0_5
The Role of IL-6 Trans-Signaling in the Pathogenesis of Perioperative Neurocognitive Disorders
Chang, O. L. B., Kim, H. S., & Maze, M. (2024) · Springer eBooks · doi:10.1007/978-3-031-32035-4_170-1
Sánchez-Guerrero, G., Chavez, D. K., Jaeschke, H., & Ramachandran, A. (2025) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.70448
The Role of IL-6 Trans-Signaling in the Pathogenesis of Perioperative Neurocognitive Disorders
Chang, O. L. B., Kim, H. S., & Maze, M. (2025) · Springer eBooks · doi:10.1007/978-3-031-73368-0_170
Borda, M., Cafaro, L., Sierra, R., Pedraza, M. D., Becerra, C., Ábalo, A., Karolewski, M. J., Cantero, M. J., Schiavone, M. A., Mazzolini, G. D., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-22097-w
Giebeler, A., & Spehr, M. (2011) · RWTH Publications (RWTH Aachen)
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
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
