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TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence
Open accessAbstract
Inhibiting acute injury–induced senescence mediated by TGFβ signaling in regenerative epithelium improves liver regeneration.
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“Similarly, transforming growth factor-β improves liver regeneration on injury by blocking paracrine senescence in neighbouring uninjured hepatocytes188.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [188]
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“While the role of paracrine senescence in cancer is yet undefined, it has been found to contribute to liver dysfunction upon acetaminophen overdose (Bird et al. 2018).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Bird et al. 2018
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“Other times, individual SASP components, such as TGF-β, might be pinpointed as disease drivers and targeting them specifically might be appropriate (Bird et al. 2018).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Bird et al. 2018
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BackgroundCellular senescence: from physiology to pathology
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“These findings contrast with previous reports in which senescence after injury in other organs may facilitate regeneration (37) and limit fibrosis after liver injury (11).”
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MethodSenescence surveillance of pre-malignant hepatocytes limits liver cancer development
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., et al. (2011) · Nature · doi:10.1038/nature10599 · Cited by 1,621
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“INTRODUCTION After moderate liver injury or resection, the liver regenerates efficiently through hepatocyte proliferation (1, 2).”
Cytoplasmic chromatin triggers inflammation in senescence and cancer
Dou, Z., Ghosh, K., Vizioli, M. G., Zhu, J., Sen, P., Wangensteen, K. J., Simithy, J., Lan, Y., Lin, Y., Zhou, Z., et al. (2017) · Nature · doi:10.1038/nature24050 · Cited by 1,335
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“In addition, study of other SASP components, which may also promote paracrine senescence after liver injury, may be worthwhile (15, 41, 42).”
Senescence in tumours: evidence from mice and humans
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“They also express a suite of senescence markers (38), including markers of the DNA damage response, growth arrest and the SASP.”
Self-citationCellular senescence drives age-dependent hepatic steatosis
Ogrodnik, M., Miwa, S., Tchkonia, T., Tiniakos, D., Wilson, C. L., Lahat, A., Day, C. P., Burt, A., Palmer, A., Anstee, Q. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15691 · Cited by 1,044
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“Fibroblast senescence occurs in the dermis after acute wounding (21) and acute myocardial infarction (22).”
mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C. J., Raguz, S., Acosta, J. C., Innes, A. J., Banito, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3225 · Cited by 788 · cited 1×
“In addition, study of other SASP components, which may also promote paracrine senescence after liver injury, may be worthwhile (15, 41, 42).”
Non-Cell-Autonomous Tumor Suppression by p53
Lujambio, A., Akkari, L., Simon, J., Grace, D., Tschaharganeh, D. F., Bolden, J. E., Zhao, Z., Thapar, V., Joyce, J. A., Krizhanovsky, V., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.020 · Cited by 766 · cited 1×
“SASP may also modulate fibrosis and regeneration in response to acute tissue injury (11, 16, 17).”
McGill, M. R., Sharpe, M. R., Williams, C. D., Taha, M., Curry, S. C., & Jaeschke, H. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59755 · Cited by 764 · cited 1×
“To investigate the functional impact of senescence in acute liver injury, we examined the established murine models of acute liver injury induced by carbon tetrachloride (CCl4) (23) or acetaminophen (24).”
BackgroundBoulter, L., Govaere, O., Bird, T. G., Radulescu, S., Ramachandran, P., Pellicoro, A., Ridgway, R. A., Seo, S. S., Spee, B., Van Rooijen, N., et al. (2012) · Nature Medicine · doi:10.1038/nm.2667 · Cited by 747 · cited 2×
“CDE- and DDC- supplemented dietary protocols were as previously described (53).”
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Targeting the TGFβ pathway for cancer therapy
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Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes.
Overturf, K., Al-Dhalimy, M., Ou, C. N., Finegold, M. J., & Grompe, M. (1997) · Europe PMC (PubMed Central) · Cited by 599
Modernizing Reference Genome Assemblies
Church, D. M., Schneider, V., Graves, T., Auger, K., Cunningham, F. M., Bouk, N., Chen, H.-C., Agarwala, R., McLaren, W. M., Ritchie, G. R. S., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001091 · Cited by 573 · cited 2×
“RNA-seq reads were aligned to the GRCm38 (57) version of the mouse genome using tophat2 version 2.1.0 (58) with Bowtie version 2.2.6.0 (59).”
MethodInfluentialAbnormal angiogenesis but intact hematopoietic potential in TGF‐β type I receptor‐deficient mice
Larsson, J., Goumans, M., Sjöstrand, L. J., van Rooijen, M. A., Ward, D., Levéen, P., Xu, X., ten Dijke, P., Mummery, C. L., & Karlsson, S. (2001) · The EMBO Journal · doi:10.1093/emboj/20.7.1663 · Cited by 563 · cited 1×
“As described previously (26), AhCre+/WT mice were crossed with both Mdm2 f l/f l and Mdm2 f l/+ mice to generate AhCre+ Mdm2 f l/f l and AhCreWT Mdm2 f l/f l and AhCre+ Mdm2 f l/+ controls and then subsequently crossed with p21KO (49) and TGFR1f l/f l (50) animals.”
Development of TGF-β signalling inhibitors for cancer therapy
Yingling, J. M., Blanchard, K. L., & Sawyer, J. S. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1580 · Cited by 557 · cited 1×
“When senescence results from oncogenic stress, it reinforces cell cycle arrest in an autocrine manner (8, 9), activates immune surveillance (10–13), and induces paracrine senescence via SASP (14, 15).”
Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration
Raven, A., Lu, W.-Y., Man, T. Y., Ferreira-Gonzalez, S., O’Duibhir, E., Dwyer, B. J., Thomson, J. P., Meehan, R. R., Bogorad, R., Koteliansky, V., et al. (2017) · Nature · doi:10.1038/nature23015 · Cited by 533 · cited 2×
“We have recently reported in an in vivo model of hepatocyte growth arrest that cholangiocytes, which expand as a ductular reaction, may act as facultative stem cells for generating hepatocytes with replacement of hepatocytes occurring over weeks to months (29).”
Self-citationNOTCH1 mediates a switch between two distinct secretomes during senescence
Hoare, M., Ito, Y., Kang, T.-W., Weekes, M. P., Matheson, N. J., Patten, D. A., Shetty, S., Parry, A. J., Menon, S., Salama, R., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3397 · Cited by 522 · cited 4×
“have shown that they appear sequentially in senescence in vitro (7).”
InfluentialHybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer
Font-Burgada, J., Shalapour, S., Ramaswamy, S., Hsueh, B., Rossell, D., Umemura, A., Taniguchi, K., Nakagawa, H., Valasek, M. A., Ye, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.026 · Cited by 486 · cited 1×
“To investigate the functional impact of senescence in acute liver injury, we examined the established murine models of acute liver injury induced by carbon tetrachloride (CCl4) (23) or acetaminophen (24).”
Hepatic progenitor cells of biliary origin with liver repopulation capacity
Lu, W.-Y., Bird, T. G., Boulter, L., Tsuchiya, A., Cole, A. M., Hay, T., Guest, R. V., Wojtacha, D., Man, T. Y., Mackinnon, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3203 · Cited by 479
Self-citationInterleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice
Kong, X., Feng, D., Wang, H., Hong, F., Bertola, A., Wang, F.-S., & Gao, B. (2012) · Hepatology · doi:10.1002/hep.25744 · Cited by 448 · cited 1×
“SASP may also modulate fibrosis and regeneration in response to acute tissue injury (11, 16, 17).”
Adult Hepatocytes Are Generated by Self-Duplication Rather than Stem Cell Differentiation
Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E., & Stanger, B. Z. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.06.003 · Cited by 426 · cited 1×
“AAV8 recombination was performed as previously described (51).”
MethodInhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis
Jamieson, T., Clarke, M., Steele, C. W., Samuel, M. S., Neumann, J., Jung, A., Huels, D., Olson, M. F., Das, S., Nibbs, R. J. B., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci61067 · Cited by 391 · cited 1×
“Genomic DNA decontamination, reverse transcription, and real-time PCR were performed using reagents and primers (QuantiFast and QuantiTect, respectively; Qiagen) on an ABI Prism 7500 cycler, except for chemokine/ chemokine receptor analysis, which was performed as previously described (55).”
MethodSelf-citationOutcomes in Adults With Acute Liver Failure Between 1998 and 2013: An Observational Cohort Study
Reuben, A., Tillman, H., Fontana, R. J., Davern, T., McGuire, B., Stravitz, R. T., Durkalski, V., Larson, A. M., Liou, I., Fix, O., et al. (2016) · Annals of Internal Medicine · doi:10.7326/m15-2211 · Cited by 390
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“We achieved this using the AhCre system (25), which expresses Cre recombinase in hepatocytes in response to administration of a xenobiotic chemical [-naphthoflavone (NF)] rendering Mdm2 inactive.”
Self-citationEndothelial Cell-Derived Angiopoietin-2 Controls Liver Regeneration as a Spatiotemporal Rheostat
Hu, J., Srivastava, K., Wieland, M. J., Runge, A., Mogler, C., Besemfelder, E., Terhardt, D., Vogel, M. J., Cao, L., Korn, C., et al. (2014) · Science · doi:10.1126/science.1244880 · Cited by 328 · cited 1×
“TGF tonically inhibits hepatocellular regeneration during health; however, changes in TGF ligand and receptor sensitivity facilitate regeneration after partial hepatectomy (44, 45).”
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302
Induction of Heart Valve Lesions by Small-Molecule ALK5 Inhibitors
Anderton, M. J., Mellor, H. R., Bell, A., Sadler, C., Pass, M., Powell, S., Steele, S. J., Roberts, R. R. A., & Heier, A. (2011) · Toxicologic Pathology · doi:10.1177/0192623311416259 · Cited by 284 · cited 5×
“Long-term therapy using TGF inhibition raises potential concerns such as carcinogenesis, autoimmunity, or cardiac valvulopathies (47).”
InfluentialAntoniades, C. G., Quaglia, A., Taams, L. S., Mitry, R. R., Hussain, M. J., Abeles, R. D., Possamai, L. A., Bruce, M., McPhail, M. J. W., Starling, C., et al. (2012) · Hepatology · doi:10.1002/hep.25657 · Cited by 281
Hubackova, S., Krejcikova, K., Bartek, J., & Hodny, Z. (2012) · Aging · doi:10.18632/aging.100520 · Cited by 272 · cited 12×
“Senescence is also marked by both a DNA damage response, which includes alterations in chromatin structure (for example, H2Ax expression), and the activation of a dynamic pro-inflammatory senescence-associated secretory phenotype (SASP) including expression of interleukin-1 (IL-1) and transforming growth factor– (TGF)…”
InfluentialJames, L. P. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfg181 · Cited by 244 · cited 1×
“Conventional treatment of acetaminophen toxicity in humans involves N-acetylcysteine therapy that, to be effective, must be given within 8 hours after exposure for humans or 4 hours for mice (34).”
Senescent Cardiac Fibroblast Is Critical for Cardiac Fibrosis after Myocardial Infarction
Zhu, F., Li, Y., Zhang, J., Piao, C., Liu, T., Li, H.-H., & Du, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074535 · Cited by 201 · cited 1×
“Fibroblast senescence occurs in the dermis after acute wounding (21) and acute myocardial infarction (22).”
Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184
Critical role of c-jun (NH2) terminal kinase in paracetamol- induced acute liver failure
Henderson, N. C., Pollock, K. J., Frew, J. W., MacKinnon, A. C., Flavell, R. A., Davis, R. J., Sethi, T., & Simpson, K. J. (2006) · Gut · doi:10.1136/gut.2006.104372 · Cited by 183 · cited 2×
“Acetaminophen was prepared as previously described (8) and delivered at 350 or 450 mg/kg by single intraperitoneal injection of 20 l/g after a 10-hour fast.”
Self-citationSenescence in chronic liver disease: Is the future in aging?
Aravinthan, A. D., & Alexander, G. J. M. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.030 · Cited by 174 · cited 1×
“It is described in both chronic diseases (19) and steatosis (20), but not in acute liver disease.”
Management of paracetamol poisoning
Ferner, R. E., Dear, J. W., & Bateman, D. N. (2011) · BMJ · doi:10.1136/bmj.d2218 · Cited by 172 · cited 1×
“Many patients present to medical services too late for this to be effective (35).”
Oe, S., Lemmer, E. R., Conner, E. A., Factor, V. M., Levéen, P., Larsson, J. T., Karlsson, S., & Thorgeirsson, S. S. (2004) · Hepatology · doi:10.1002/hep.20426 · Cited by 125 · cited 1×
“TGF is believed to restrict hepatocellular regeneration rather than just acting as a brake during the termination phase of liver regeneration (1, 46).”
Sasaki, M., Miyakoshi, M., Sato, Y., & Nakanuma, Y. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.03.008 · Cited by 112 · cited 1×
“SASP components including chemokines (for example, CCL2/CCR2 and CX3CL1/CX3CR1) that promote macrophage recruitment and local TGF expression within areas of necrosis are well described in human fulminant hepatic failure (33, 48).”
Houck, K. A., & Michalopoulos, G. K. (1989) · Journal of Cellular Physiology · doi:10.1002/jcp.1041410308 · Cited by 89 · cited 1×
“TGF tonically inhibits hepatocellular regeneration during health; however, changes in TGF ligand and receptor sensitivity facilitate regeneration after partial hepatectomy (44, 45).”
Parallel pathways in RAF-induced senescence and conditions for its reversion
Jeanblanc, M., Ragu, S., Gey, C., Contrepois, K., Courbeyrette, R., Thuret, J., & Mann, C. (2011) · Oncogene · doi:10.1038/onc.2011.481 · Cited by 74 · cited 1×
“A similarly rapid senescence program (including TGF production, direct Notch target activation, and p16 expression) has been observed in OIS models within 48 hours in vitro (7, 39).”
The intestinal epithelium compensates for p53-mediated cell death and guarantees organismal survival
Valentin-Vega, Y. A., Okano, H., & Lozano, G. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.109 · Cited by 58 · cited 1×
“To exclude any extrahepatic effects of AhCre-mediated recombination (including the intestinal epithelium) (28), we used a hepatocyte-specific induction regime using an adeno-associated viral vector, AAV8–TBG (thyroxine binding globulin)–Cre, to induce hepatocyte-specific deletion of Mdm2 (29).”
MethodBartholin, L., Cyprian, F. S., Vincent, D. F., Garcia, C., Martel, S., Horvat, B., Berthet, C., Goddard‐Léon, S., Treilleux, I., Rimokh, R., et al. (2008) · genesis · doi:10.1002/dvg.20425 · Cited by 56 · cited 4×
“Here, we used LSL-TGFR1-CA mice, which have a genetically inducible constitutively active (CA) TGFR1 that is expressed upon removal of a stop codon (LSL) by Cre recombinase (30).”
InfluentialSelf-citationRole of transforming growth factor beta 1 on hepatic regeneration and apoptosis in liver diseases.
Takiya, S., Tagaya, T., TAKAHASHI, K., Kawashima, H., Kamiya, M., Fukuzawa, Y., Kobayashi, S., Fukatsu, A., Kato, Y., & Kakumu, S. (1995) · Journal of Clinical Pathology · doi:10.1136/jcp.48.12.1093 · Cited by 53 · cited 1×
“In acute liver failure, TGF is produced in the injured liver (43).”
Wlodzimirow, K. A., Eslami, S., Chamuleau, R. A. F. M., Nieuwoudt, M., & Abu–Hanna, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050952 · Cited by 48 · cited 1×
“Validated clinical scoring systems predict the outcomes of patients who will survive versus those in whom liver regeneration will ultimately fail (36), suggesting a tipping point beyond which recovery is unlikely.”
Induction of p53 Renders ATM-Deficient Mice Refractory to Hepatocarcinogenesis
Teoh, N., Pyakurel, P., Dan, Y. Y., Swisshelm, K. L., Hou, J. Y., Mitchell, C., Fausto, N., Gu, Y., & Farrell, G. C. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.11.008 · Cited by 39 · cited 1×
“Hepatocyte senescence involves the induction of genes encoding p53 (TRP53), p21 (WAF1), and p16 (INK4A) (18).”
Cole, A. M., Ridgway, R. A., Derkits, S., Parry, L., Barker, N., Clevers, H. C., Clarke, A. R., & Sansom, O. J. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000101 · Cited by 35 · cited 1×
“As described previously (26), AhCre+/WT mice were crossed with both Mdm2 f l/f l and Mdm2 f l/+ mice to generate AhCre+ Mdm2 f l/f l and AhCreWT Mdm2 f l/f l and AhCre+ Mdm2 f l/+ controls and then subsequently crossed with p21KO (49) and TGFR1f l/f l (50) animals.”
Self-citationA rapid strategy to detect the recombined allele in LSL‐TβRICA transgenic mice
Vincent, D. F., Kaniewski, B., Powers, S. E., Havenar‐Daughton, C., Marie, J. C., Wotton, D., & Bartholin, L. (2010) · genesis · doi:10.1002/dvg.20653 · Cited by 17
Self-citationForbes, S. J., Themis, M., Alison, M. R., Shiota, A., Kobayashi, T., Coutelle, C. C., & Hodgson, H. J. F. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301143 · Cited by 15 · cited 1×
“Using a mitogen cocktail consisting of hepatocyte growth factor (HGF) and triodothyronine (T3) (27), we attempted to promote proliferation of senescent hepatocytes in the Mdm2Hep model but were unable to do so, unlike in wild-type hepatocytes (fig.”
Self-citation
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“A number of hepatocytes undergo senescence upon acute acetaminophen (APAP) induced liver damage [253].”
BackgroundEvasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases
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Metadata
- Authors
- Bird, T. G., Müller, M., Boulter, L., Vincent, D. F., Ridgway, R. A., Lopez-Guadamillas, E., Lu, W.-Y., Jamieson, T., Govaere, O., Campbell, A. D., Ferreira-Gonzalez, S., Cole, A. M., Hay, T., Simpson, K. J., Clark, W., Hedley, A., Clarke, M., Gentaz, P., Nixon, C., Bryce, S., Kiourtis, C., Sprangers, J., Nibbs, R. J. B., Van Rooijen, N., Bartholin, L., McGreal, S. R., Apte, U., Barry, S. T., Iredale, J. P., Clarke, A. R., Serrano, M., Roskams, T. A., Sansom, O. J., & Forbes, S. J.
- Affiliations
- MRC Centre for Regenerative Medicine (GB)
- Cancer Research UK Scotland Institute (GB)
- Spanish National Cancer Research Centre (ES)
- Universitair Ziekenhuis Leuven (BE)
- Medical Research Council (MRC) Centre for Regenerative Medicine, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
- Cardiff University (GB)
- University of Glasgow (GB)
- Vrije Universiteit Medical Center, Department of Molecular Cell Biology, Van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands.
- Lyon 1 Université (FR)
- University of Kansas Medical Center (US)
- AstraZeneca (United Kingdom) (GB)
- University of Bristol (GB)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Bird, Thomas G.
- Clarke, Alan R.
- ORCID
- Bird, Thomas G.
- Müller, Miryam
- Boulter, Luke
- Vincent, David F.
- Ridgway, Rachel A.
- Lopez-Guadamillas, Elena
- Lu, Wei-Yu
- Jamieson, Thomas
- Govaere, Olivier
- Campbell, Andrew D.
- Ferreira-Gonzalez, Sofía
- Cole, Alicia M.
- Hay, Trevor
- Clark, William
- Hedley, Ann
- Clarke, Mairi
- Gentaz, Pauline
- Nixon, Colin
- Bryce, Steven
- Kiourtis, Christos
- Nibbs, Robert J. B.
- Van Rooijen, Nico
- Bartholin, Laurent
- McGreal, Steven R.
- Apte, Udayan
- Barry, Simon T.
- Iredale, John P.
- Clarke, Alan R.
- Serrano, Manuel
- Roskams, Tania A.
- Sansom, Owen J.
- Forbes, Stuart J.
- Venue
- Science Translational Medicine
- Published
- 2018-08-15
- Volume
- 10
- Issue
- 454
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC6420144
- OpenAlex
- W2887276938
- Cited by
- 261
- References
- 61
- Citations by year
- 2026: 16 · 2025: 34 · 2024: 47 · 2023: 42 · 2022: 31 · 2021: 28 · 2020: 37 · 2019: 24 · 2018: 2
- FWCI
- 14.26
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, other-oa)
- Bristol Research (University of Bristol) (publishedVersion, other-oa)
- Explore Bristol Research (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (R01 DK98414)
- Wellcome Trust (107492Z, 081604AIA)
- Medical Research Council (G1000868, G0900992)
- Cancer Research UK (2016-CRUK core running, A12481)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- acute liver injury, liver regeneration, hepatocyte senescence, paracrine senescence, TGF-β1, acetaminophen toxicity, p21, macrophages, hepatocyte proliferation, acute liver failure
- MeSH terms
- Animals, Disease Models, Animal, Humans, Liver, Liver Regeneration, Macrophages, Male, Mice, Inbred C57BL, Necrosis, Signal Transduction, Transforming Growth Factor beta, Cellular Senescence, Paracrine Communication, Hepatocytes, Cyclin-Dependent Kinase Inhibitor p21
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