A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.
Open accessAbstract
The liver has a remarkable regenerative capacity, allowing recovery following injury. Regeneration after injury is contingent on maintenance of healthy residual liver mass, otherwise fulminant hepatic failure (FHF) may arise. Understanding the protective mechanisms safeguarding hepatocytes and promoting their proliferation is critical for devising therapeutic strategies for FHF. We demonstrate that A20 is part of the physiological response of hepatocytes to injury. In particular, A20 is significantly upregulated in the liver following partial hepatectomy. A20 protects hepatocytes from apoptosis and ongoing inflammation by inhibiting NF-κB. Hepatic expression of A20 in BALB/c mice dramatically improves survival following extended and radical lethal hepatectomy. A20 expression in the liver limits hepatocellular damage hence maintains bilirubin clearance and the liver synthetic function. In addition, A20 confers a proliferative advantage to hepatocytes via decreased expression of the cyclin-dependent kinase inhibitor p21waf1. In conclusion , A20 provides a proliferative advantage to hepatocytes. By combining anti-inflammatory, antiapoptotic and pro-proliferative functions, A20-based therapies could be beneficial in prevention and treatment of FHF. (Hepatology 2005;42:156–164.)
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A20 is induced in mice and humans as part of the hepatocyte's regenerative response following hepatectomy.
“A20, a newly identified player in LR, is induced in mice and humans as part of the hepatocyte’s regenerative response following hepatectomy (15, 20).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
The Results section reports a 13-fold rise in A20 mRNA in mouse liver 24 hours after hepatectomy, and the Discussion identifies A20 as part of the hepatocyte regenerative response. The paper does not show A20 induction after hepatectomy in humans; its reference to human A20 mRNA concerns a gene introduced into mouse livers. (LLM, conf=0.90)
Experimental — accuracy not yet measuredShort-term overexpression of A20 does not carry a significant carcinogenic risk.
“Our previous studies however indicate that short-term overexpression of A20 does not carry a significant carcinogenic risk. Indeed, no rAd.A20 treated mice developed liver carcinomas during the 6 months monitoring period (14–16).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
The Discussion says limited rAd-mediated A20 expression may avoid tumor formation and reports no liver neoplasia in treated mice during long-term follow-up. The Results section specifies that surviving mice were monitored for eight weeks, not the six months stated in the citing sentence; this paper therefore does not support that duration. (LLM, conf=0.87)
Experimental — accuracy not yet measuredNo rAd.A20 treated mice developed liver carcinomas during the 6 months monitoring period.
“no rAd.A20 treated mice developed liver carcinomas during the 6 months monitoring period (14–16).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
The section “Mice Engineered to Express A20 Are Protected From Lethality Following Extended and Radical Hepatectomy” reports no liver tumors among surviving mice, including those treated with rAd.A20. However, it says they were monitored for 8 weeks, not 6 months; the longer monitoring period is unsupported. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThe extended hepatectomy mouse model is characterized by delayed liver regeneration and a high lethality rate of 50%.
“the mouse model of EH, characterized by delayed LR and high lethality rate (50%), as to magnify A20’s pro-proliferative mechanism(s) (15).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
In “Mice Engineered to Express A20 Are Protected From Lethality Following Extended and Radical Hepatectomy” (page unavailable), the paper reports 50% survival after extended hepatectomy in noninfected mice, equivalent to 50% lethality in that group. The proliferation results show an advantage for A20-treated mice, but do not establish that liver regeneration in the extended-hepatectomy model was delayed relative to a standard hepatectomy model. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHepatocyte cultures transduced with rAd. at MOI 50-200 pfu/cell lead to transgene expression in >95% of cells without toxicity.
“Hepatocyte cultures (60% confluent) were transduced with rAd. at a multiplicity of infection (MOI) of 50–200 plaque-forming units per cell (pfu/cell), leading to transgene expression in >95% of cells without toxicity (14, 15) (Fig. S1).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
The Cell Culture and Cell Lines section (page unavailable) reports rAd infection of mouse hepatocytes at 25 pfu/cell, with transgene expression in more than 98% of cells and minimal toxicity. It does not support the cited 50–200 pfu/cell dose or 60% confluence, and “minimal toxicity” is not the same as no toxicity. (LLM, conf=0.90)
Experimental — accuracy not yet measured
A20 has established pro-proliferative properties in hepatocytes, in part through decreasing p21.
“A20, a potent anti-inflammatory and NF-κB inhibitory protein, has established pro-proliferative properties in hepatocytes, in part through decreasing expression of the Cyclin Dependent Kinase Inhibitor, p21.”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
The Results section reports greater proliferation and lower p21 expression in A20-expressing mouse hepatocytes. The Discussion says A20 promotes proliferation *likely* through reduced p21 expression; the claim presents that proposed mechanism as established. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA20 exerts multiple hepatoprotective functions through combined anti-inflammatory, anti-apoptotic, and pro-proliferative effects in hepatocytes.
“We previously demonstrated that A20/tnfaip3, a key element of the cellular response to injury and inflammation (12, 13), exerts multiple hepatoprotective functions through combined anti-inflammatory, anti-apoptotic, and pro-proliferative effects in hepatocytes (14–16).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
Overexpression of A20 improves liver regeneration and survival in mouse models of extended and lethal hepatectomy in part through decreasing p21.
“Overexpression of A20 dramatically improves LR and survival in mouse models of extended (78%) and lethal (87%) hepatectomy in part through decreasing the expression of CDKI, p21 (15).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
The rAd. dose and route of administration achieves maximal transgene expression in 30% of hepatocytes, 5 days after injection.
“This dose and route of administration achieves maximal transgene expression in 30% of hepatocytes, 5 days after injection (15).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
The NMuLi cell line responds in a physiologic manner to growth factor-induced cell cycle progression.
“This cell line responds in a physiologic manner to growth factor-induced cell cycle progression (15).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [15]
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Cites
A Model to Predict Survival in Patients With End–Stage Liver Disease
Kamath, P. S., Wiesner, R. H., Malinchoc, M., Kremers, W. K., Therneau, T. M., Kosberg, C. L., D’Amico, G., Dickson, R. E., & Kim, W. R. (2001) · Hepatology · doi:10.1053/jhep.2001.22172 · Cited by 4,989 · see citing works
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133 · see citing works
An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
Beg, A. A., & Baltimore, D. (1996) · Science · doi:10.1126/science.274.5288.782 · Cited by 3,047 · see citing works
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828 · see citing works
Suppression of TNF-α-Induced Apoptosis by NF-κB
Antwerp, D. J. V., Martin, S. J., Kafri, T., Green, D. R., & Verma, I. M. (1996) · Science · doi:10.1126/science.274.5288.787 · Cited by 2,581 · see citing works
TNF- and Cancer Therapy-Induced Apoptosis: Potentiation by Inhibition of NF-κB
Wang, C.-Y., Mayo, M. W., & Baldwin, A. S. (1996) · Science · doi:10.1126/science.274.5288.784 · Cited by 2,581 · see citing works
IκB: a Specific Inhibitor of the NF-κB Transcription Factor
Baeuerle, P. A., & Baltimore, D. (1988) · Science · doi:10.1126/science.3140380 · Cited by 2,154 · see citing works
De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling
Wertz, I. E., O’Rourke, K. M., Zhou, H., Eby, M. T., Aravind, L., Seshagiri, S., Wu, P., Wiesmann, C., Baker, R. T., Boone, D. L., et al. (2004) · Nature · doi:10.1038/nature02794 · Cited by 1,852 · see citing works
Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB
Beg, A. A., Sha, W. C., Bronson, R. T., Ghosh, S., & Baltimore, D. (1995) · Nature · doi:10.1038/376167a0 · Cited by 1,828 · 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
Failure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M., Lodolce, J. P., & Ma, A. (2000) · Science · doi:10.1126/science.289.5488.2350 · Cited by 1,409 · see citing works
Fausto, N. (2000) · Journal of Hepatology · doi:10.1016/s0168-8278(00)80412-2 · Cited by 1,022 · see citing works
Severe Liver Degeneration in Mice Lacking the IκB Kinase 2 Gene
Li, Q., Antwerp, D. V., Mercurio, F., Lee, K., & Verma, I. M. (1999) · Science · doi:10.1126/science.284.5412.321 · Cited by 963 · 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
del Olmo, J. A., Peña, A., Serra, M. Á., Wassel, A., Benages, A., & Rodrigo, J. M. (2000) · Journal of Hepatology · doi:10.1016/s0168-8278(01)68827-5 · Cited by 895 · see citing works
Targets of the cyclin-dependent kinase Cdk1
Ubersax, J. A., Woodbury, E. L., Quang, P. N., Paraz, M., Blethrow, J. D., Shah, K., Shokat, K. M., & Morgan, D. O. (2003) · Nature · doi:10.1038/nature02062 · Cited by 892 · see citing works
Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration.
Fausto, N., Laird, A., & Webber, E. M. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.15.8529831 · Cited by 620 · see citing works
Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia
S, M. G. B., Raper, S. E., Kozarsky, K., Stein, E. A., Engelhardt, J. F., Muller, D. W., Lupien, P. J., & Wilson, J. M. (1994) · Nature Genetics · doi:10.1038/ng0494-335 · Cited by 558 · see citing works
Lee, W. M. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312163292508 · Cited by 544 · see citing works
NFkappaB prevents apoptosis and liver dysfunction during liver regeneration.
Iimuro, Y., Nishiura, T., Hellerbrand, C., Behrns, K. E., Schoonhoven, R., Grisham, J. W., & Brenner, D. A. (1998) · Journal of Clinical Investigation · doi:10.1172/jci483 · Cited by 447 · see citing works
The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity.
Opipari, A. W., Hu, H., Yabkowitz, R., & Dixit, V. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42292-2 · Cited by 434 · see citing works
Lieber, A., He, C. Y., Meuse, L. A., Schowalter, D., Kirillova, I., Winther, B., & Kay, M. A. (1997) · Journal of Virology · doi:10.1128/jvi.71.11.8798-8807.1997 · Cited by 412 · see citing works
Acute liver failure: Clinical features, outcome analysis, and applicability of prognostic criteria
Shakil, A. O., Kramer, D. J., Mazariegos, G. V., Fung, J. J., & Rakela, J. (2000) · Liver Transplantation · doi:10.1002/lt.500060218 · Cited by 349 · see citing works
Long-Term Results of Pediatric Liver Transplantation
Goss, J. A., Shackleton, C. R., McDiarmid, S. V., Maggard, M. A., Swenson, K., Seu, P., Vargas, J., Martin, M., Ament, M. E., Brill, J. E., et al. (1998) · Annals of Surgery · doi:10.1097/00000658-199809000-00014 · Cited by 283 · see citing works
Greenbaum, 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
A20 Blocks Endothelial Cell Activation through a NF-κB-dependent Mechanism
Cooper, J. T., Stroka, D. M., Brostjan, C., Palmetshofer, A., Bach, F. H., & Ferran, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.18068 · Cited by 247 · see citing works
Self-citationSass, D. A., & Shakil, A. O. (2005) · Liver Transplantation · doi:10.1002/lt.20435 · Cited by 243 · 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
Complete reconstitution of mouse liver with xenogeneic hepatocytes.
Rhim, J. A., Sandgren, E. P., Palmiter, R. D., & Brinster, R. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4942 · Cited by 216 · see citing works
A20 Inhibits Cytokine-Induced Apoptosis and Nuclear Factor κB–Dependent Gene Activation in Islets
Grey, S. T., Arvelo, M. B., Hasenkamp, W. M., Bach, F. H., & Ferran, C. J. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.8.1135 · Cited by 208 · see citing works
Self-citationButenas, S., Mann, & Butenas, S. (2002) · Biochemistry (Moscow) · doi:10.1023/a:1013985911759 · Cited by 204 · 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 · see citing works
Albrecht, J. H., Poon, R. Y. C., Ahonen, C. L., Rieland, B. M., Deng, C., & Crary, G. S. (1998) · Oncogene · doi:10.1038/sj.onc.1201728 · Cited by 198 · see citing works
Tumor necrosis factor α in the pathogenesis of human and murine fulminant hepatic failure
Streetz, K. L., Leifeld, L., Grundmann, D., Ramakers, J., Eckert, K., Spengler, U., Brenner, D. A., Manns, M. P., & Trautwein, C. (2000) · Gastroenterology · doi:10.1053/gast.2000.9364 · Cited by 197 · see citing works
Erhardt, P., & Cooper, G. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17601 · Cited by 190 · see citing works
Panis, Y. H., McMullan, D. M., & Emond, J. C. (1997) · Surgery · doi:10.1016/s0039-6060(97)90283-x · Cited by 183 · see citing works
Lo, C., Fan, S.-T., Chan, J. K. F., Wei, W., Lo, R. J. W., & Lai, C. (1996) · Transplantation · doi:10.1097/00007890-199609150-00029 · Cited by 158 · see citing works
Trey, C., Lipworth, L., Chalmers, T. C., Davidson, C. S., Gottlieb, L. S., Pópper, H., & Saunders, S. J. (1968) · New England Journal of Medicine · doi:10.1056/nejm196810102791504 · Cited by 158 · see citing works
Ferran, C. J., Stroka, D., Badrichani, A. Z., Cooper, J. T., Wrighton, C. J., Soares, M. P., Grey, S. T., & Bach, F. H. (1998) · Blood · doi:10.1182/blood.v91.7.2249 · Cited by 157 · see citing works
Self-citationA20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis
Arvelo, M. B., Cooper, J. T., Longo, C., Daniel, S., Grey, S. T., Mahiou, J., Czismadia, E., Abu-Jawdeh, G., & Ferran, C. (2002) · Hepatology · doi:10.1053/jhep.2002.31309 · Cited by 147 · see citing works
Self-citationNF-κB/Rel/IκB: Implications in gastrointestinal diseases
Schmid, R. M., & Adler, G. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)70374-x · Cited by 139 · see citing works
Daniel, S., Arvelo, M. B., Patel, V. I., Longo, C. R., Shrikhande, G., Shukri, T., Mahiou, J., Sun, D. W., Mottley, C., Grey, S. T., et al. (2004) · Blood · doi:10.1182/blood-2003-02-0635 · Cited by 132 · see citing works
Self-citationSun, Z., Klein, A. S., Radaeva, S., Hong, F., El-Assal, O. N., Pan, H.-N., Jaruga, B., Bátkai, S., Hoshino, S., Tian, Z., et al. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00696-6 · Cited by 126 · see citing works
Galun, E., Zeira, E., Pappo, O., Peters, M., & Rose-John, S. (2000) · The FASEB Journal · doi:10.1096/fj.99-0913com · Cited by 124 · see citing works
Albrecht, J. H., Meyer, A., & Hu, M. Y. (1997) · Hepatology · doi:10.1002/hep.510250311 · Cited by 116 · see citing works
In vivo hepatocyte proliferation is inducible through a TNF and IL-6-independent pathway
Ledda-Columbano, G. M., Curto, M., Piga, R., Zedda, A. I., Menegazzi, M., Sartori, C., Shinozuka, H., Bluethmann, H., Poli, V, Ciliberto, G., et al. (1998) · Oncogene · doi:10.1038/sj.onc.1202018 · Cited by 96 · see citing works
Timchenko, N. A. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.13.3293 · Cited by 72 · see citing works
Human liver regeneration: Hepatic energy economy is less efficient when the organ is diseased
Mann, D. V., Lam, W. W. M., Hjelm, M., So, N. M. C., Yeung, D. K. W., Metreweli, C., & Lau, W. Y. (2001) · Hepatology · doi:10.1053/jhep.2001.27012 · Cited by 70 · see citing works
Kwon, Y. H., Jovanović, A., Serfas, M. S., & Tyner, A. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300996200 · Cited by 43 · see citing works
Serfas, M. S., Goufman, E., Feuerman, M. H., Gartel, A. L., & Tyner, A. L. (1997) · PubMed · Cited by 39 · see citing works
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Research works printed but not linked: 6
- Opipari AJ, Hu HM, Yabkowitz R, Dixit VM. The A20 zinc finger protein protects cells from TNF cytotoxicity. J Biol Chem 1992;267:12424- 12427.
- Arvelo MB, Cooper JT, Longo C, Daniel S, Grey ST, Mahiou J, et al. A20 protects mice from galactosmine/lipopolysaccharide acute toxic lethal hep- atitis. HEPATOLOGY 2002;35:535-543.
- Ferran C, Stroka DM, Badrichani AZ, Cooper JT, Wrighton CJ, Soares M, et al. A20 inhibits NF-B activation in endothelial cells without sensi- tizing to TNF-mediated apoptosis. Blood 1998;91:2249-2258.
- Schmid RM, Adler G. NF-kappaB/rel/IkappaB: implications in gastroin- testinal diseases. Gastroenterology 2000;118:1208-1228.
- Sun Z, Klein AS, Radaeva S, Hong F, El-Assal O, Pan HN, et al. In vitro interleukin-6 treatment prevents mortality associated with fatty liver trans- plants in rats. Gastroenterology 2003;125:202-215.
- Bonham CA, Gerber DA, Grewal H. Live donor transplantation: Strate- gies for expanding the adult organ donor pool. Conference report 2001;1st Annual Winter Symposium: Living donor adult-to-adult transplantation of the kidney and liver.
Cited by
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Catrysse, L., Vereecke, L., Beyaert, R., & Loo, G. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.10.005 · Cited by 494 · see citing works
Wullaert, A., Loo, G., Heyninck, K., & Beyaert, R. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0031 · Cited by 217 · see citing works
Mechanisms of crosstalk between TNF-induced NF-κB and JNK activation in hepatocytes
Wullaert, A., Heyninck, K., & Beyaert, R. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.003 · Cited by 200 · see citing works
Zhang, P., Wang, P., Zhao, L., Zhang, X., Ji, Y., Zhang, X., Fang, C., Lu, Y., Yang, X., Gao, M.-M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4453 · Cited by 189 · 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
What is critical for liver surgery and partial liver transplantation
Clavien, P., Oberkofler, C. E., Raptis, D. A., Lehmann, K., Rickenbacher, A., & El‐Badry, A. M. (2010) · Hepatology · doi:10.1002/hep.23713 · Cited by 121 · see citing works
Smad6 inhibits non-canonical TGF-β1 signalling by recruiting the deubiquitinase A20 to TRAF6
Jung, S. M., Lee, J.-H., Park, J., Oh, Y. S., Lee, S. K., Park, J. S., Lee, J. Y., Kim, J. H., Lee, J. Y., Bae, Y., et al. (2013) · Nature Communications · doi:10.1038/ncomms3562 · Cited by 104 · see citing works
A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells
Vendrell, J. A., Ghayad, S. E., Larbi, S. B., Dumontet, C., Mechti, N., & Cohen, P. A. (2007) · Oncogene · doi:10.1038/sj.onc.1210269 · Cited by 93 · see citing works
Interleukin-6 inhibits oxidative injury and necrosis after extreme liver resection
Jin, X., Zhang, Z., Beer–Stolz, D., Zimmers, T. A., & Koniaris, L. G. (2007) · Hepatology · doi:10.1002/hep.21728 · Cited by 85 · see citing works
Li, L., Guo, J., Chen, Y., Chang, C., & Xu, C. (2017) · BMC Genomics · doi:10.1186/s12864-016-3476-6 · Cited by 83 · 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
Self-citationA20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death
Catrysse, L., Ghahremani, M., Vereecke, L., Youssef, S., Guire, C. M., Sze, M., Weber, A., Heikenwalder, M., de Bruin, A., Beyaert, R., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.154 · Cited by 71 · see citing works
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Solhi, R., Lotfinia, M., Gramignoli, R., Najimi, M., & Vosough, M. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.06.002 · Cited by 71 · see citing works
Chen, H., Hu, L., Luo, Z., Zhang, J., Zhang, C., Qiu, B., Dong, L., Tan, Y., Ding, J., Tang, S., et al. (2015) · Molecular Cancer · doi:10.1186/s12943-015-0454-6 · Cited by 58 · see citing works
De Jonge, J., Kurian, S., Shaked, A., Reddy, K. R., Hancock, W., Salomon, D. R., & Olthoff, K. M. (2009) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2009.02557.x · Cited by 54 · see citing works
Ramsey, H. E., Da Silva, C. G., Longo, C. R., Csizmadia, E., Studer, P., Patel, V. I., Damrauer, S. M., Siracuse, J. J., Daniel, S., & Ferran, C. (2009) · Liver Transplantation · doi:10.1002/lt.21879 · Cited by 46 · see citing works
Self-citationMicroRNAs in Liver Regeneration
Chen, X., Zhao, Y., Wang, F., Bei, Y., Xiao, J., & Yang, C. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000430381 · Cited by 44 · see citing works
Hong, J., Bae, W. ‐., Yi, J.-K., Kim, G., & Kim, E. ‐. (2015) · Journal of Periodontal Research · doi:10.1111/jre.12332 · 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
A20 Modulates Lipid Metabolism and Energy Production to Promote Liver Regeneration
Damrauer, S. M., Studer, P., da Silva, C. G., Longo, C. R., Ramsey, H. E., Csizmadia, E., Shrikhande, G., Scali, S. T., Libermann, T. A., Bhasin, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017715 · Cited by 37 · see citing works
Self-citationMele, A. A., Revuelta‐Cervantes, J., Chien, V., Friedman, D. J., & Ferran, C. J. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0398-6_10 · Cited by 35 · see citing works
Self-citationPreclinical models of acute liver failure: a comprehensive review
Hefler, J., Marfil‐Garza, B. A., Pawlick, R. L., Freed, D. H., Karvellas, C. J., Bigam, D. L., & Shapiro, A. M. J. (2021) · PeerJ · doi:10.7717/peerj.12579 · 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
Nicotinamide induces liver regeneration and improves liver function by activating SIRT1
Wan, H., Li, J., Liao, H., Liao, M., Luo, L., Xu, L., Yuan, K., & Zeng, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9688 · Cited by 28 · see citing works
Aggravation of post-ischemic liver injury by overexpression of A20, an NF-κB suppressor
Yu, J., Lee, H., Lee, S., Yu, H., Moon, W. S., Chung, M. J., Park, J., & Park, B. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.11.029 · Cited by 27 · see citing works
New gene therapy strategies for hepatic fibrosis
Salazar-Montes, A. M. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i13.3813 · Cited by 26 · see citing works
Galectin-1 is essential for efficient liver regeneration following hepatectomy
Potikha, T., Ella, E., Cerliani, J. P., Mizrahi, L., Pappo, O., Rabinovich, G. A., Galun, E., & Goldenberg, D. (2016) · Oncotarget · doi:10.18632/oncotarget.9194 · Cited by 26 · see citing works
A20 Attenuates Liver Fibrosis in NAFLD and Inhibits Inflammation Responses
Wang, X., Ai, L., Xu, Q., Wu, C. W., Chen, Z., Su, D., Jiang, X., & Fan, Z. (2017) · Inflammation · doi:10.1007/s10753-017-0528-2 · Cited by 24 · see citing works
Studer, P., da Silva, C. G., Revuelta‐Cervantes, J., Mele, A. A., Csizmadia, E., Siracuse, J. J., Damrauer, S. M., Peterson, C. R., Candinas, D., Stroka, D., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.52 · Cited by 22 · see citing works
Self-citationChen, S., Xing, H., Li, S., Yu, J., Li, H., Liu, S., Tian, Z., Tang, K., Rao, Q., Wang, M., et al. (2015) · Leukemia Research · doi:10.1016/j.leukres.2015.06.004 · Cited by 22 · see citing works
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Ai, L., Xu, Q., Wu, C. W., Wang, X., Chen, Z., Su, D., Jiang, X., Xu, A., Lin, Q., & Fan, Z. (2015) · International Journal of Biological Sciences · doi:10.7150/ijbs.13371 · Cited by 21 · see citing works
Lappas, M. (2017) · Molecular Human Reproduction · doi:10.1093/molehr/gax041 · Cited by 21 · see citing works
Pinna, F., Bissinger, M., Beuke, K., Huber, N., Longerich, T., Kummer, U., Schirmacher, P., Sahle, S., & Breuhahn, K. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00610 · Cited by 21 · see citing works
Plock, J. A., Frese, S., Keogh, A., Bisch-Knaden, S., Ayuni, E., Corazza, N., Weikert, C., Jakob, S. M., Erni, D., Dufour, J., et al. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.04.016 · Cited by 21 · see citing works
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da Silva, C. G., Revuelta‐Cervantes, J., Studer, P., & Ferran, C. J. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0398-6_8 · Cited by 20 · see citing works
Self-citationCell-ECM Interactions in Repair and Regeneration
Petreaca, M. L., & Martins‐Green, M. M. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-381422-7.10002-1 · Cited by 18 · see citing works
Long, C., Xie, N., Shu, Y., Wu, Y., He, P., Zhou, Y., Xiang, Y., Gu, J., Yang, L., & Wang, Y. (2021) · Medical Science Monitor · doi:10.12659/msm.931236 · Cited by 15 · 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
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Yang, J. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i27.3537 · Cited by 12 · see citing works
Emerging role of zinc finger protein A20 as a suppressor of hepatocellular carcinoma
Yi, P., Shu, Y., Bi, W., Zheng, X. B., Feng, W., He, L., & Li, J. S. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28877 · Cited by 12 · see citing works
A20 Expressing Tumors and Anticancer Drug Resistance
da Silva, C. G., Minussi, D. C., Ferran, C. J., & Bredel, M. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0398-6_5 · Cited by 11 · see citing works
Self-citationXu, H., Wang, L., Zheng, P., Liu, Y., Zhang, C., Jiang, K., Song, H., & Ji, G. (2017) · Oncotarget · doi:10.18632/oncotarget.17153 · Cited by 11 · see citing works
Jia, F., Deng, F., Xu, P., Li, S., Wang, X., Hu, P., Ren, H., Tong, S., & Yin, W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.603192 · Cited by 10 · see citing works
Translational Studies of A20 in Atherosclerosis and Cardiovascular Disease
McGillicuddy, F. C., Moll, H. P., Farouk, S. S., Damrauer, S. M., Ferran, C. J., & Reilly, M. P. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0398-6_6 · Cited by 9 · see citing works
Self-citationQin, Y., Zhang, Z., Yu, L., He, J., Hou, Y., Liu, T., Wu, J., Wu, S.-H., & Guo, L. (2006) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00403.x · Cited by 9 · see citing works
Xu, M., Yan, L., Gou, X.-H., Li, D., Huang, Y., Hu, H., Wang, L., & Han, L. (2008) · Journal of Surgical Research · doi:10.1016/j.jss.2008.04.029 · Cited by 9 · see citing works
A20 reduces lipid storage and inflammation in hypertrophic adipocytes via p38 and Akt signaling
Ai, L., Wang, X., Chen, Z., Lin, Q., Su, D., Xu, Q., Wu, C. W., Jiang, X., Xu, A., & Fan, Z. (2016) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-016-2768-0 · Cited by 9 · see citing works
Watakabe, K., Miyoshi, M., Kakinuma, S., Sato, A., Tsuchiya, J., Shimizu, T., Mochida, T., Inada, K., Kaneko, S., Kawai‐Kitahata, F., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202400109r · Cited by 8 · see citing works
Zinc finger protein A20 inhibits maturation of dendritic cells resident in rat liver allograft
Dai, F., Yang, J., Chen, X., & Xu, M. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2013.01.062 · Cited by 7 · see citing works
de Jonge, J., & Olthoff, K. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-34062-5.00006-6 · Cited by 4 · see citing works
A20 Attenuates Lipopolysaccharide-Induced Inflammation Through MAPK/ERK/JNK Pathway in LX-2 Cells
Wang, X., Han, F., Shen, Y., Chen, Y., & Ji, Z. (2021) · Hepatitis Monthly · doi:10.5812/hepatmon.114050 · Cited by 2 · see citing works
Cell–ECM Interactions in Repair and Regeneration
Petreaca, M. L., & Martins‐Green, M. M. (2008) · Elsevier eBooks · doi:10.1016/b978-012369410-2.50007-3 · Cited by 2 · see citing works
Cell–ECM Interactions in Repair and Regeneration
Petreaca, M. L., & Martins‐Green, M. M. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-385942-6.00017-2 · Cited by 2 · see citing works
Hypothermia predicts hepatic failure after extensive hepatectomy in mice
Ohashi, N., Hori, T., Üemoto, S., Jermanus, S., Chen, F., Nakao, A., & Nguyen, J. H. (2013) · World Journal of Hepatology · doi:10.4254/wjh.v5.i4.170 · Cited by 1 · see citing works
Factors associated with outcome of liver surgery and hepatocellular carcinoma
Alkozai, E. M. (2016) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Xenotransplantation 1.0 to 2.0
Haque, O. J., Cloonan, D. J., McIntosh, E. E., & Ferran, C. J. (2020) · Springer eBooks · doi:10.1007/978-3-030-55244-2_18
Self-citationExtended 78% Hepatectomy in a Mouse Surgical Model
Brennan, P., Patel, N., Aridi, T. G., Zhan, M., Angolano, C., & Ferran, C. J. (2024) · Journal of Visualized Experiments · doi:10.3791/66528
Self-citation
- Authors
- Longo, C. R., Patel, V. I., Shrikhande, G. V., Scali, S. T., Csizmadia, E., Daniel, S., Sun, D. W., Grey, S. T., Arvelo, M. B., & Ferran, C.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Ferran, Christiane
- Venue
- Hepatology
- Published
- 2005-07
- Volume
- 42
- Issue
- 1
- Pages
- 156-164
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2025002041
- Cited by
- 60
- References
- 52
- Citations by year
- 2024: 2 · 2023: 1 · 2021: 8 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 7 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- Funders
- Beth Israel Deaconess Medical Center
- Association pour la Recherche sur le Cancer
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health (NIH T32, DK063275, T32 HL 07734)
- National Heart, Lung, and Blood Institute (T32 HL-07734)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063275)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- A20, radical hepatectomy, acute liver failure, hepatocyte proliferation, p21, NF-κB signaling, hepatocyte apoptosis, liver regeneration, liver injury, inflammation, bilirubin clearance, liver synthetic function
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