Role of STAT3 in liver regeneration: survival, DNA synthesis, inflammatory reaction and liver mass recovery
Open accessAbstract
The hepatoprotective effect of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) has been well documented. However, reports on the role of IL-6/STAT3 in liver regeneration are conflicting probably due to the fact that the model of Stat3 knockout mice were complicated with obesity and fatty liver, which may cause some secondary effects on liver regeneration. To study the direct role of STAT3 and to circumvent the problems of obesity and fatty liver in liver regeneration, we generated conditional STAT3 knockout in the liver (L-Stat3(-/-)) using a transthyretin-driven Cre-lox method. The L-Stat3(-/-) mice were born with the expected Mendelian frequency and showed no obesity or other obvious phenotype. After partial hepatectomy, mortality in the L-Stat3(-/-) mice was significantly higher than the littermate Stat3(f/+) controls in the early time points (<24 h). Hepatocyte DNA synthesis in the survived L-Stat3(-/-) mice slightly decreased as compared with Stat3(f/+) mice at 40 h after partial hepatectomy, whereas similar hepatocyte DNA synthesis was found at other time points and liver mass could be completely recovered in the L-Stat3(-/-) mice. In another model of liver regeneration induced by subcutaneous injection of carbon tetrachloride (CCl(4)), hepatocyte DNA synthesis in the CCl(4)-treated L-Stat3(-/-) mice also decreased as compared with Stat3(f/+) mice at 40 h after injection but not at other time points. In addition, infiltration of neutrophils and monocyte increased in the liver of CCl(4)-treated L-Stat3(-/-) mice compared to wild-type mice. In conclusion, STAT3 is required for survival in the acute stage after 70% hepatectomy and plays a role in inflammatory reaction after hepatocyte necrosis. However, the hepatocytic STAT3 may have limited role in liver mass recovery although DNA synthesis may be impaired.
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Successful liver regeneration depends on an intact TNF-NFκB-IL-6-STAT3 pathway.
“Successful LR depends on an intact TNF-NFκB-IL-6-STAT3 pathway.”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [29]
The Abstract reports that surviving mice lacking liver STAT3 completely recovered liver mass after partial hepatectomy. The Conclusion (page not provided) says STAT3 is required for survival in the acute stage but plays a limited role in subsequent DNA synthesis and liver-mass recovery. Thus, the paper does not support an intact STAT3 pathway as a requirement for successful liver regeneration. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredHepatocyte-specific STAT3 knockout causes insulin resistance and impaired liver regeneration.
“Insulin resistance; impaired liver regeneration”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Moh et al., 2007
The Abstract and the section on liver-mass restoration report higher early mortality and a slight, temporary decrease in hepatocyte DNA synthesis after liver-specific STAT3 deletion. They also report complete liver-mass recovery, so they do not support a general claim of impaired regeneration. Our copy does not report insulin resistance (searched: “insulin resistance”). Page numbers were unavailable. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe effect of liver-specific Stat3 deletion on liver regeneration was relatively modest.
“By contrast, the effect of liver-specific Stat3 deletion was relatively modest (71, 72)”
From Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2 (2022) · cites this paper as [72]
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Cites
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828 · see citing works
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 1,536 · see citing works
Fausto, N., Campbell, J. S., & Riehle, K. J. (2006) · Hepatology · doi:10.1002/hep.20969 · Cited by 1,378 · see citing works
Targeted disruption of the mouse <i>Stat3</i> gene leads to early embryonic lethality
Takeda, K., Noguchi, K., Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., & Akira, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3801 · Cited by 1,323 · see citing works
Interleukin-6: from basic science to medicine--40 years in immunology.
Kishimoto, T. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115806 · Cited by 1,083 · see citing works
Cytokines and the hepatic acute phase response
Moshage, H. (1997) · Journal of Pathology · doi:10.1002/(sici)1096-9896(199703)181:3 · Cited by 1,035 · see citing works
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 · see citing works
Radaeva, S., Sun, R., Pan, H., Hong, F., & Gao, B. (2004) · Hepatology · doi:10.1002/hep.20184 · Cited by 638 · see citing works
Self-citationPositional cloning: Let's not call it reverse anymore
Collins, F. S. (1992) · Nature Genetics · doi:10.1038/ng0492-3 · Cited by 479 · see citing works
Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo
Inoue, H., Ogawa, W., Ozaki, M., Haga, S., Matsumoto, M., Furukawa, K., Hashimoto, N., Kido, Y., Mori, T., Sakaue, H., et al. (2004) · Nature Medicine · doi:10.1038/nm980 · Cited by 384 · see citing works
Roles of STAT3 defined by tissue-specific gene targeting
Akira, S. (2000) · Oncogene · doi:10.1038/sj.onc.1203478 · Cited by 345 · see citing works
Alonzi, T., Maritano, D., Gorgoni, B., Rizzuto, G., Libert, C., & Poli, V. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.5.1621-1632.2001 · Cited by 329 · see citing works
STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration
Li, W., Liang, X., Kellendonk, C., Poli, V., & Taub, R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202807200 · Cited by 307 · cited 10× · see citing works
“01 between the L-Stat3 / and Stat3f/+ mice. www.laboratoryinvestigation.org | Laboratory Investigation | Volume 87 October 2007 1023 0 10 20 30 40 50 60 70 24 40 48 72 Time after PH (hr) B rd U p os iti ve n uc le i ( % ) * WT L-Stat3-/- DAPI Brdu Merge 3 days 60 days WT L-Stat3-/- Figure 4 Liver regeneration after PH…”
InfluentialOpposing roles of STAT1 and STAT3 in T cell–mediated hepatitis: regulation by SOCS
Hong, F., Jaruga, B., Kim, W. H., Radaeva, S., El-Assal, O. N., Tian, Z., Nguyen, V.-A., & Gao, B. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15841 · Cited by 291 · see citing works
Self-citationGreenbaum, L. E., Li, W., Cressman, D. E., Peng, Y., Ciliberto, G., Poli, V, & Taub, R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3135 · Cited by 270 · see citing works
Selzner, M., & Clavien, P. (2000) · Hepatology · doi:10.1002/hep.510310108 · Cited by 253 · see citing works
Yang, S. Q., Lin, H. Z., Mandal, A. K., Huang, J., & Diehl, A. M. (2001) · Hepatology · doi:10.1053/jhep.2001.28054 · Cited by 237 · see citing works
Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms
Haga, S., Terui, K., Zhang, H. Q., Enosawa, S., Ogawa, W., Inoue, H., Okuyama, T., Takeda, K., Akira, S., Ogino, T., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17970 · Cited by 237 · see citing works
Wu, H., Wade, M., Krall, L., Grisham, J., Xiong, Y., & Van Dyke, T. (1996) · Genes & Development · doi:10.1101/gad.10.3.245 · Cited by 234 · see citing works
Hepatoprotection via the IL-6/Stat3 pathway
Taub, R. A. (2003) · Journal of Clinical Investigation · doi:10.1172/jci19974 · Cited by 217 · see citing works
Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration.
Fitzgerald, M. J., Webber, E. M., Donovan, J. R., & Fausto, N. (1995) · PubMed · Cited by 213 · see citing works
Interleukin 6 Is Important for Survival After Partial Hepatectomy in Mice
Blindenbacher, A., Wang, X., Langer, I., Savino, R., Terracciano, L., & Heim, M. H. (2003) · Hepatology · doi:10.1053/jhep.2003.50378 · Cited by 202 · cited 1× · see citing works
“However, increasing evidence suggests that IL-6 plays more important role in protection against liver injury, and only a minor role in liver regeneration.(5,6) Several transcription factors are activated shortly after PH or toxic liver injury, including NF-kB, signal transducer and activator of transcription 3 (STAT3)…”
Klein, C., Wüstefeld, T., Assmus, U., Roskams, T., Rose-John, S., Müller, M., Manns, M. P., Ernst, M., & Trautwein, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200523640 · Cited by 200 · see citing works
Interleukin-6/Glycoprotein 130-dependent Pathways Are Protective during Liver Regeneration
Wüestefeld, T., Klein, C., Streetz, K. L., Betz, U. A. K., Lauber, J., Buer, J., Manns, M. P., Müller, W., & Trautwein, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208470200 · Cited by 176 · see citing works
Yan, C., Costa, R. H., Darnell, J. E., Jr., Chen, J. D., & Dyke, T. A. V. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb08184.x · Cited by 151 · see citing works
Tewari, M., Dobrzański, P., Mohn, K. L., Cressman, D. E., Hsu, J., Bravo, R., & Taub, R. A. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.6.2898 · Cited by 150 · see citing works
Rana, B., Xie, Y., Mischoulon, D., Bucher, N. L. R., & Farmer, S. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.30.18123 · Cited by 149 · see citing works
Interferon-α activates multiple STAT signals and down-regulates c-Met in primary human hepatocytes
Radaeva, S., Jaruga, B., Hong, F., Kim, W., Fan, S., Cai, H., Strom, S. C., Liu, Y., El-Assal, O. N., & Gao, B. (2002) · Gastroenterology · doi:10.1053/gast.2002.32388 · Cited by 128 · see citing works
Self-citationSoprano, D., Soprano, K., & Goodman, D. (1986) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.83.19.7330 · Cited by 114 · see citing works
Haga, S., Ogawa, W., Inoue, H., Terui, K., Ogino, T., Igarashi, R., Takeda, K., Akira, S., Enosawa, S., Furukawa, H., et al. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.03.027 · Cited by 108 · see citing works
Makover, A., Soprano, D. R., Wyatt, M. L., & Goodman, D. S. (1989) · Differentiation · doi:10.1111/j.1432-0436.1989.tb00809.x · Cited by 83 · see citing works
Tissue-specific inactivation of p53 tumor suppression in the mouse.Preprint
Bowman, T., Symonds, H., Gu, L., Yin, C., Oren, M., & Dyke, T. V. (1996) · Genes & Development · doi:10.1101/gad.10.7.826 · Cited by 80 · see citing works
Costa, R. H., Dyke, T. A. V., Yan, C., Kuo, F. C., & Darnell, J. E., Jr. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.17.6589 · Cited by 77 · see citing works
Interaction of alcohol and hepatitis viral proteins
Gao, B. (2002) · Alcohol · doi:10.1016/s0741-8329(02)00201-x · Cited by 37 · see citing works
Self-citationSpecific activation of AP‐1 but not Stat3 in regenerating liver in mice
Heim, M. H., Gamboni, G., Beglinger, C., & Gyr, K. (1997) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1997.2100770.x · Cited by 34 · see citing works
In Vitroandin VivoStudies on Transthyretin Oligomerization
Bellovino, D., Morimoto, T., Pisaniello, A., & Gaetani, S. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4137 · Cited by 14 · see citing works
Flagged first, then by citations
3 of the 39 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Bellovino D, Morimoto T, Pisaniello A, et al. In vitro and in vivo studies on transthyretin oligomerization. Exp Cell Res 1998;243:101-112.
Cited by
Sorted by citations
Reparative inflammation takes charge of tissue regeneration
Karin, M., & Clevers, H. (2016) · Nature · doi:10.1038/nature17039 · Cited by 767 · see citing works
The intestinal microbiota regulates body composition through NFIL3 and the circadian clock
Wang, Y., Kuang, Z., Yu, X., Ruhn, K. A., Kubo, M., & Hooper, L. V. (2017) · Science · doi:10.1126/science.aan0677 · Cited by 456 · see citing works
Establishment, maintenance, and recall of inflammatory memory
Larsen, S. B., Cowley, C. J., Sajjath, S. M., Barrows, D., Yang, Y., Carroll, T. S., & Fuchs, E. V. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.07.001 · Cited by 321 · see citing works
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
Regulation of liver regeneration by growth factors and cytokines
Böhm, F., Köhler, U. A., Speicher, T., & Werner, S. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000085 · Cited by 275 · see citing works
Signal Transducer and Activator of Transcription 3 in Liver Diseases: A Novel Therapeutic Target
Wang, H., Lafdil, F., Kong, X., & Gao, B. (2011) · International Journal of Biological Sciences · doi:10.7150/ijbs.7.536 · Cited by 268 · see citing works
Self-citationThe microbiota coordinates diurnal rhythms in innate immunity with the circadian clock
Brooks, J. F., Behrendt, C. L., Ruhn, K. A., Lee, S., Raj, P., Takahashi, J. S., & Hooper, L. V. (2021) · Cell · doi:10.1016/j.cell.2021.07.001 · Cited by 230 · see citing works
STAT3 in the Systemic Inflammation of Cancer Cachexia
Zimmers, T., Fishel, M., & Bonetto, A. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.02.009 · Cited by 216 · see citing works
CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy
Huseni, M. A., Wang, L., Klementowicz, J. E., Yuen, K. C. Y., Bréart, B., Orr, C., Liu, L.-F., Li, Y., Gupta, V., Li, C., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100878 · Cited by 192 · see citing works
STAT proteins – Key regulators of anti-viral responses, inflammation, and tumorigenesis in the liver
Gao, B., Wang, H., Lafdil, F., & Feng, D. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.01.029 · Cited by 179 · see citing works
Self-citationAcute inflammation stimulates a regenerative response in the neonatal mouse heart
Han, C., Nie, Y., Lian, H., Liu, R., He, F., Huang, H., & Hu, S. (2015) · Cell Research · doi:10.1038/cr.2015.110 · Cited by 169 · see citing works
STAT3 pathway in cancers: Past, present, and future
Wang, H., Man, Q., Huo, F., Gao, X., Lin, H., Li, S.-R., Wang, J., Su, F., Cai, L., Shi, Y., et al. (2022) · MedComm · doi:10.1002/mco2.124 · Cited by 172 · see citing works
Self-citationRegulating billions of blood platelets: glycans and beyond
Grozovsky, R., Giannini, S., Falet, H., & Hoffmeister, K. M. (2015) · Blood · doi:10.1182/blood-2015-01-569129 · Cited by 154 · see citing works
STAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury
Paris, A. J., Hayer, K. E., Oved, J. H., Avgousti, D. C., Toulmin, S. A., Zepp, J. A., Zacharias, W. J., Katzen, J. B., Basil, M. C., Kremp, M. M., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0569-x · Cited by 148 · see citing works
Lu, X., Cao, X., Zhu, Y., Wu, Z., Zhuang, X., Shao, M., Xu, Q., Zhou, Y., Ji, H., Lu, Q.-R., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0428-x · Cited by 146 · see citing works
Genetic determinants of hepatic steatosis in man
Hooper, A. J., Adams, L. A., & Burnett, J. R. (2011) · Journal of Lipid Research · doi:10.1194/jlr.r008896 · Cited by 142 · see citing works
Li, L., Cui, L., Lin, P., Liu, Z., Bao, S., Ma, X., Nan, H., Zhu, W., Cen, J., Mao, Y., et al. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.01.009 · Cited by 134 · see citing works
Role of platelets on liver regeneration after 90% hepatectomy in mice
Myronovych, A., Murata, S., Chiba, M., Matsuo, R., Ikeda, O., Watanabe, M., Hisakura, K., Nakano, Y., Kohno, K., Kawasaki, T., et al. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.04.019 · Cited by 131 · see citing works
Cross-talk between KLF4 and STAT3 regulates axon regeneration
Qin, S., Zou, Y., & Zhang, C. (2013) · Nature Communications · doi:10.1038/ncomms3633 · Cited by 130 · see citing works
Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis
Zhou, M., Yang, H., Learned, R. M., Tian, H., & Ling, L. (2017) · Nature Communications · doi:10.1038/ncomms15433 · Cited by 123 · see citing works
A regulatory T cell Notch4–GDF15 axis licenses tissue inflammation in asthma
Harb, H., Victor, E. S., Crestani, E., Benamar, M., Massoud, A. H., Cui, Y., Charbonnier, L., Arbag, S. N., Barış, S., Cunnigham, A., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0777-3 · Cited by 123 · see citing works
Petty, A. J., Dai, R., Lapalombella, R., Baiocchi, R. A., Benson, D. M., Li, Z., Huang, X., & Yang, Y. (2021) · JCI Insight · doi:10.1172/jci.insight.146707 · Cited by 115 · see citing works
p38 MAPK: A dual role in hepatocyte proliferation through reactive oxygen species
Tormos, A. M., Taléns‐Visconti, R., Nebreda, Á. R., & Sastre, J. (2013) · Free Radical Research · doi:10.3109/10715762.2013.821200 · Cited by 110 · see citing works
Izumi, T., Imai, J., Yamamoto, J., Kawana, Y., Endo, A., Sugawara, H., Kohata, M., Asai, Y., Takahashi, K., Kodama, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07747-0 · Cited by 109 · see citing works
IL-22 is involved in liver regeneration after hepatectomy
Ren, X., Hu, B., & Colletti, L. M. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00075.2009 · Cited by 109 · see citing works
Liver Injury and Regeneration: Current Understanding, New Approaches, and Future Perspectives
Hora, S., & Wüestefeld, T. (2023) · Cells · doi:10.3390/cells12172129 · Cited by 104 · see citing works
Kindlin-2 preserves integrity of the articular cartilage to protect against osteoarthritis
Wu, X., Lai, Y., Chen, S., Zhou, C., Tao, C., Fu, X., Li, J., Huang, J., Tong, W., 田洪涛, et al. (2022) · Nature Aging · doi:10.1038/s43587-021-00165-w · Cited by 98 · see citing works
Self-citationZhang, H., Madi, A., Yosef, N., Chihara, N., Awasthi, A., Pot, C., Lambden, C., Srivastava, A., Burkett, P. R., Nyman, J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108433 · Cited by 91 · see citing works
Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2
Cheng, N., Kim, K.-H., & Lau, L. F. (2022) · JCI Insight · doi:10.1172/jci.insight.158207 · Cited by 87 · see citing works
“By contrast, the effect of liver-specific Stat3 deletion was relatively modest (71, 72), suggesting that Yap may play a more important role than Stat3 in”
Wang, X., Yang, C., Wang, X., Miao, J., Chen, W., Zhou, Y., Xu, Y., An, Y., Cheng, A., Ye, W., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.028 · Cited by 84 · see citing works
Self-citationSuppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability
Wang, L., Astone, M., Alam, S. K., Zhu, Z., Pei, W., Frank, D., Burgess, S., & Hoeppner, L. H. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.049029 · Cited by 8 · see citing works
Genetically modified mouse models for the study of nonalcoholic fatty liver disease
Nagarajan, P. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i11.1141 · Cited by 79 · see citing works
Hackett, A. R., Lee, D.-H., Dawood, A., Rodriguez, M., Funk, L. H., Tsoulfas, P., & Lee, J. K. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.01.017 · Cited by 78 · see citing works
da Silva, C. G., Studer, P., Skroch, M., Mahiou, J., Minussi, D. C., Peterson, C. R., Wilson, S. W., Patel, V. I., Ma, A., Csizmadia, E., et al. (2013) · Hepatology · doi:10.1002/hep.26197 · Cited by 77 · see citing works
Ching, C. B., Gupta, S., Li, B., Cortado, H. H., Mayne, N. R., Jackson, A. R., McHugh, K. M., & Becknell, B. (2018) · Kidney International · doi:10.1016/j.kint.2017.12.006 · Cited by 73 · see citing works
An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction
Sun, J.-Y., Du, L., Shi, X., Zhang, Y., Liu, Y., Wang, Y.-L., Chen, B., Liu, T., Zhu, H., Liu, Y., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade4110 · Cited by 76 · see citing works
Distinctive role of inflammation in tissue repair and regeneration
Choi, B., Lee, C., & Yu, J. (2023) · Archives of Pharmacal Research · doi:10.1007/s12272-023-01428-3 · Cited by 75 · see citing works
Anti-inflammatory and anti-apoptotic roles of endothelial cell STAT3 in alcoholic liver injury
Miller, A. M., Wang, H., Park, O., Horiguchi, N., Lafdil, F., Mukhopadhyay, P., Moh, A., Fu, X.-Y., Kunos, G., Pacher, P., et al. (2010) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2009.01141.x · Cited by 64 · see citing works
Self-citationMechanisms and biomarkers of liver regeneration after drug-induced liver injury
Clemens, M. M., McGill, M. R., & Apte, U. M. (2019) · Advances in pharmacology · doi:10.1016/bs.apha.2019.03.001 · Cited by 67 · see citing works
Novel mechanisms of platelet clearance and thrombopoietin regulation
Grozovsky, R., Giannini, S., Falet, H., & Hoffmeister, K. M. (2015) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000170 · Cited by 66 · see citing works
Hénique, C., Bollée, G., Loyer, X., Grahammer, F., Dhaun, N., Camus, M., Vernerey, J., Guyonnet, L., Gaillard, F., Lazareth, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01885-7 · Cited by 57 · see citing works
IL-22 resolves MASLD via enterocyte STAT3 restoration of diet-perturbed intestinal homeostasis
Zhang, P., Liu, J., Lee, A. A., Tsaur, I., Ohira, M., Duong, V., Vo, N., Watari, K., Su, H., Kim, J. Y., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.08.012 · Cited by 60 · see citing works
Kim, J. H., Qu, A., Reddy, J. K., Gao, B., & Gonzalez, F. J. (2013) · Hepatology · doi:10.1002/hep.26683 · Cited by 57 · see citing works
Self-citationOh, R. S., Haak, A. J., Smith, K. M. J., Ligresti, G., Choi, K. M., Xie, T., Wang, S., Walters, P., Thompson, M. A., Freeman, M., et al. (2018) · Journal of Cell Science · doi:10.1242/jcs.209932 · Cited by 55 · see citing works
Kohjima, M., Tsai, T.-H., Tackett, B. C., Thevananther, S., Li, L., Chang, B. H.-J., & Chan, L. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.07.025 · Cited by 54 · see citing works
Genetic variants in STAT3 are associated with nonalcoholic fatty liver disease
Sookoian, S. C., Castaño, G. O., Gianotti, T. F., Gemma, C., Rosselli, M. S., & Pirola, C. J. (2008) · Cytokine · doi:10.1016/j.cyto.2008.08.001 · Cited by 54 · see citing works
Maternal hepatic growth response to pregnancy in the mouse
Dai, G., Bustamante, J. J., Zou, Y., Myronovych, A., Bao, Q., Kumar, S., & Soares, M. J. (2011) · Experimental Biology and Medicine · doi:10.1258/ebm.2011.011076 · Cited by 54 · see citing works
STAT3 Sensitizes Insulin Signaling by Negatively Regulating Glycogen Synthase Kinase-3β
Moh, A., Zhang, W., Yu, S. S. B., Wang, J., Xu, X., Li, J., & Fu, X.-Y. (2008) · Diabetes · doi:10.2337/db06-1582 · Cited by 54 · see citing works
Self-citationChen, X., Meng, Q., Wang, C., Liu, Q., Sun, H., Huo, X., Sun, P., Yang, X., Peng, J., & Liu, K. (2014) · Pharmaceutical Research · doi:10.1007/s11095-014-1483-3 · Cited by 53 · see citing works
STAT3 but not STAT4 is critical for γδT17 cell responses and skin inflammation
Agerholm, R., Rizk, J., Viñals, M. T., & Bekiaris, V. (2019) · EMBO Reports · doi:10.15252/embr.201948647 · Cited by 52 · see citing works
GABA, γ-Aminobutyric Acid, Protects Against Severe Liver Injury
Hata, T., Rehman, F. K., Hori, T., & Nguyen, J. H. (2018) · Journal of Surgical Research · doi:10.1016/j.jss.2018.11.047 · Cited by 50 · see citing works
NK Cell IL-10 Production Requires IL-15 and IL-10 Driven STAT3 Activation
Clark, S. E., Burrack, K. S., Jameson, S. C., Hamilton, S. E., & Lenz, L. L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02087 · Cited by 45 · see citing works
Boles, M. K., Wilkinson, B. M., Wilming, L. G., Liu, B., Probst, F. J., Harrow, J., Grafham, D. V., Hentges, K. E., Woodward, L. P., Maxwell, A., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000759 · Cited by 44 · see citing works
The IL-22–oncostatin M axis promotes intestinal inflammation and tumorigenesis
Cineus, R., Luo, Y., Saliutina, M., Manna, S., Cancino, C., Blázquez, L. V., Wang, L., Bösel, D., Abdelrahman, A., Klementowicz, J. E., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02149-z · Cited by 43 · see citing works
Transforming growth factor‐β in liver cancer stem cells and regeneration
Rao, S., Zaidi, S., Banerjee, J., Jogunoori, W., Sebastian, R., Mishra, B., Nguyen, B.-N. H., Wu, R.-C., White, J. C., Deng, C.-X., et al. (2017) · Hepatology Communications · doi:10.1002/hep4.1062 · Cited by 38 · see citing works
Allonso, D., Belgrano, F. S., Calzada, N., Guzmán, M. G., Vázquez, S., & Mohana‐Borges, R. (2012) · Journal of Clinical Virology · doi:10.1016/j.jcv.2012.07.010 · Cited by 41 · see citing works
Su, Y., Zhang, W., Patro, C. P. K., Zhao, J., Mu, T., Ma, Z., Xu, J., Ban, K. H.-K., Yi, C., & Zhou, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00362 · Cited by 41 · see citing works
Self-citationWang, H., Park, O., Lafdil, F., Shen, K., Horiguchi, N., Yin, S., Fu, X.-Y., Kunos, G., & Gao, B. (2009) · Hepatology · doi:10.1002/hep.23430 · Cited by 41 · see citing works
Self-citationMeng, Q., Chen, X., Wang, C., Liu, Q., Sun, H., Sun, P., Huo, X., Liu, Z., & Liu, K. (2015) · Food & Function · doi:10.1039/c5fo00082c · Cited by 39 · see citing works
Hepatocyte growth control by SOCS1 and SOCS3
Khan, M. G. M., Ghosh, A., Variya, B. C., Santharam, M. A., Kandhi, R., Ramanathan, S., & Ilangumaran, S. (2019) · Cytokine · doi:10.1016/j.cyto.2019.154733 · Cited by 37 · see citing works
Kumar, A., Lualdi, M., Lyozin, G. T., Sharma, P., Lončarek, J., Fu, X.-Y., & Kuehn, M. R. (2014) · Developmental Biology · doi:10.1016/j.ydbio.2014.12.016 · Cited by 38 · see citing works
Self-citationShen, K., Zheng, S.-S., Park, O., Wang, H., Sun, Z., & Gao, B. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00554.2007 · Cited by 37 · see citing works
Self-citationYadav, P., Singh, S. K., Rajput, S., Allawadhi, P., Khurana, A., Weiskirchen, R., & Navik, U. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108563 · Cited by 36 · see citing works
Kim, A. R., I1 Park, J., Oh, H. T., Kim, K. M., Hwang, J., Jeong, M. G., Kim, E., Hwang, E. S., & Hong, J. (2019) · The FASEB Journal · doi:10.1096/fj.201801256rr · Cited by 35 · see citing works
Cai, Z., Simons, D. L., Fu, X.-Y., Feng, G.-S., Wu, S. M., & Zhang, X. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05054-11 · Cited by 34 · see citing works
Self-citationKostromina, E. Y., Petersen, N., Wang, X., Lim, C.-Y., Radda, G. K., Li, C., & Han, W. (2010) · Endocrinology · doi:10.1210/en.2009-1199 · Cited by 34 · see citing works
Liver Regeneration and Immunity: A Tale to Tell
Di-Iacovo, N., Pieroni, S., Piobbico, D., Castelli, M., Scopetti, D., Ferracchiato, S., Fazia, M. A. D., & Servillo, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021176 · Cited by 36 · see citing works
Intrahepatic T‐Cell Receptor β Immune Repertoire Is Essential for Liver Regeneration
Liang, Q. D., Liu, Z., Zhu, C., Wang, B., Liu, X., Yang, Y., Lv, X., Mu, H., & Wang, K. (2018) · Hepatology · doi:10.1002/hep.30067 · Cited by 32 · see citing works
Hypothalamic Control of Hepatic Glucose Production and Its Potential Role in Insulin Resistance
Buettner, C., & Camacho, R. C. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.09.001 · Cited by 31 · see citing works
Systems Analysis of the Complement-Induced Priming Phase of Liver Regeneration
Min, J. S., DeAngelis, R. A., Reis, E. S., Gupta, S., Maurya, M. R., Evans, C. R., Das, A. K., Burant, C., Lambris, J. D., & Subramaniam, S. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600628 · Cited by 29 · see citing works
Liu, N. Q., Lin, Y., Li, L., Lu, J., Geng, D., Zhang, J., Jashashvili, T., Buser, Z., Magallanes, J., Tassey, J., et al. (2022) · Communications Biology · doi:10.1038/s42003-021-02944-y · Cited by 28 · see citing works
Obayashi, Y., Arisaka, H., Yoshida, S., Mori, M., & Takahashi, M. (2012) · Amino Acids · doi:10.1007/s00726-012-1317-8 · Cited by 28 · see citing works
Tob1 is a constitutively expressed repressor of liver regeneration
Ho, K. J., Do, N. L., Otu, H. H., Dib, M. J., Ren, X., Enjyoji, K., Robson, S. C., Terwilliger, E. F., & Karp, S. J. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20092434 · Cited by 27 · see citing works
Qiu, X., Zhou, J.-Q., Xu, H., Li, Y.-Y., Ma, S.-D., Qiao, H., Zeng, K., Wang, Q.-Q., Ouyang, J., Liu, Y.-H., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.07.012 · Cited by 25 · see citing works
Zhou, J., Chong, P. S. Y., Lu, X., Cheong, L.-L., Bi, C., Liu, S.-C., Zhou, Y., Tan, T. Z., Yang, H. H., Chung, T., et al. (2014) · Experimental Hematology · doi:10.1016/j.exphem.2014.08.001 · Cited by 23 · see citing works
Stat3 Regulates Liver Progenitor Cell-Driven Liver Regeneration in Zebrafish
Khaliq, M., Ko, S., Liu, Y., Wang, H., Sun, Y., Solnica‐Krezel, L., & Shin, D. (2018) · Gene Expression · doi:10.3727/105221618x15242506133273 · Cited by 25 · see citing works
Reisinger, S. N., Sideromenos, S., Horváth, O., Derdak, S. V., Cicvaric, A., Monje, F. J., Bilban, M., Häring, M., Glat, M. J., & Pollak, D. D. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00904-2 · Cited by 23 · see citing works
Autonomic nervous system network and liver regeneration
Kamimura, K., Inoue, R., Nagoya, T., Sakai, N., Goto, R., Ko, M., Niwa, Y., & Terai, S. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i15.1616 · Cited by 23 · see citing works
Regulation of Signal Transduction and Role of Platelets in Liver Regeneration
Nowatari, T., Fukunaga, K., & Ohkohchi, N. (2012) · International Journal of Hepatology · doi:10.1155/2012/542479 · Cited by 21 · see citing works
Wang, N., Yang, C., Sun, Z.-Z., Wang, X., & Chen, S. (2010) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2010.10.017 · Cited by 19 · see citing works
Jiao, Y., Ye, D. Z., Li, Z., Teta‐Bissett, M., Peng, Y., Taub, R. A., Greenbaum, L. E., & Kaestner, K. H. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00084.2014 · Cited by 18 · see citing works
Ma, J., Xia, S., Zhang, B., Luo, F., Guo, L., Yang, Y., Gong, H., & Yan, M. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154893 · Cited by 17 · see citing works
Zhang, Y. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i6.2081 · Cited by 17 · see citing works
Tmub1 negatively regulates liver regeneration via inhibiting STAT3 phosphorylation
Fu, H., Dong, R., Zhang, Y., Xu, J., Liu, M., & Chen, P. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2018.12.013 · Cited by 17 · see citing works
Huang, P. C., Huo, Y., Lou, X., Li, H., Barnstable, C. J., Zhang, C., & Zhang, S. S.-M. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.06.015 · Cited by 17 · see citing works
Self-citationInflammatory liver diseases and susceptibility to sepsis
Lü, H. (2024) · Clinical Science · doi:10.1042/cs20230522 · Cited by 17 · see citing works
Long Non-Coding RNAs in Liver Cancer and Nonalcoholic Steatohepatitis
Uchida, S., & Kauppinen, S. (2020) · Non-Coding RNA · doi:10.3390/ncrna6030034 · Cited by 16 · see citing works
Prosurvival role of JAK/STAT and Akt signaling pathways in MPP+-induced apoptosis in neurons
Junyent, F., Alvira, D., Yeste‐Velasco, M., de la Torre, A. V., Beas‐Zárate, C., Sureda, F. X., Folch, J., Pallàs, M., Camins, A., & Verdaguer, E. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.08.015 · Cited by 16 · see citing works
Hao, L., Zhong, W. H., Sun, X., & Zhou, Z. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.709002 · Cited by 15 · see citing works
Inoue, R., Kamimura, K., Nagoya, T., Sakai, N., Yokoo, T., Goto, R., Ogawa, K., Shinagawa‐Kobayashi, Y., Watanabe‐Mori, Y., Sakamaki, A., et al. (2018) · FEBS Open Bio · doi:10.1002/2211-5463.12382 · Cited by 14 · see citing works
RetractedOgiso, H., Ito, H., Kanbe, A., Ando, T., Hara, A., Shimizu, M., Moriwaki, H., & Seishima, M. (2017) · Digestive Diseases and Sciences · doi:10.1007/s10620-017-4651-6 · Cited by 13 · see citing works
Modulatory effects of NDP-MSH in the regenerating liver after partial hepatectomy in rats
Lonati, C., Carlin, A., Leonardi, P., Valenza, F., Bòsari, S., Catania, A. P., & Gatti, S. (2013) · Peptides · doi:10.1016/j.peptides.2013.10.014 · Cited by 13 · see citing works
Liver regeneration accelerates hepatitis B virus‐related tumorigenesis of hepatocellular carcinoma
Teng, C., Chang, H., Tsai, H., Hsieh, W., Kuo, Y., Su, I., & Lin, Y. (2018) · Molecular Oncology · doi:10.1002/1878-0261.12318 · Cited by 12 · see citing works
Dynamic Changes in pStat3 Are Involved in Meiotic Spindle Assembly in Mouse Oocytes
Haraguchi, S., Ikeda, M., Akagi, S., & Hirao, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041220 · Cited by 9 · see citing works
Kasper, P., Selle, J., Vohlen, C., Wilke, R., Kuiper-Makris, C., Klymenko, O., Bae‐Gartz, I., Schömig, C., Quaas, A., Schumacher, B., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105609 · Cited by 11 · see citing works
Sulczewski, F. B., Martino, L. A., Salles, D., Yamamoto, M. M., Rosa, D. S., & Boscardin, S. B. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1006996 · Cited by 11 · see citing works
Type I IFN receptor blockade alleviates liver fibrosis through macrophage-derived STAT3 signaling
Park, S.-J., Garcia Diaz, J., Comlekoglu, T., & Hahn, Y. S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1528382 · Cited by 10 · see citing works
Hu, K., Xu, J., Fan, K., Zhou, D., Li, L., Tang, L. P., Peng, X., Zhang, L., & Wang, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117561 · Cited by 10 · see citing works
Chen, X., Xu, C., Zhang, F., & Ma, J. (2010) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2009.0111 · Cited by 10 · see citing works
Wen, X., Huan, H.-B., Wang, X., Chen, X., Wu, L., Zhang, Y., Liu, W., Bie, P., & Xia, F. (2016) · Biomedical Materials · doi:10.1088/1748-6041/11/6/065007 · Cited by 10 · see citing works
- Authors
- Moh, A., Iwamoto, Y., Chai, G.-X., Zhang, S. S.-M., Kano, A., Yang, D. D., Zhang, W., Wang, J., Jacoby, J. J., Gao, B., Flavell, R. A., & Fu, X.-Y.
- Affiliations
- Indiana University School of Medicine (US)
- Yale University (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fu, Xin-Yuan
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 87
- Issue
- 10
- Pages
- 1018-1028
- ISSN
- 0023-6837 (ISSN-L)
- OpenAlex
- W2090563155
- Cited by
- 147
- References
- 39
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 5 · 2023: 14 · 2022: 9 · 2021: 13 · 2020: 13 · 2019: 8 · 2018: 11 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 9 · 2012: 7
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Yale University
- National Institutes of Health (5r01ar044906-05, DK34989)
- U.S. Army
- National Institute of Allergy and Infectious Diseases (R01AI34522, R01AI034522)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-34989, P30DK034989)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR-44906)
- Yale Liver Center (DK34989)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- STAT3, liver regeneration, interleukin-6, partial hepatectomy, carbon tetrachloride, hepatocyte DNA synthesis, hepatocyte viability, liver inflammation, neutrophil infiltration, monocyte infiltration, liver necrosis
- MeSH terms
- Animals, Carbon Tetrachloride, Digestive System, Disease Models, Animal, DNA, Hepatectomy, Inflammation, Liver, Liver Regeneration, Gene Deletion, Mice, Knockout, Integrases, Hepatocytes, Hepatic Insufficiency, STAT1 Transcription Factor, STAT3 Transcription Factor, Mice
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