Role of liver regeneration in the repair of liver injury induced by N-acetyl-p-aminophenol

Yinkang MO; Zihao FAN; Feng REN

doi:10.12449/JCH240929

Volume 40 Issue 9

Sep. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(9): 1902-1907

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Role of liver regeneration in the repair of liver injury induced by N-acetyl-p-aminophenol

DOI: 10.12449/JCH240929

Beijing Institute of Hepatology，Beijing YouAn Hospital，Capital Medical University，Beijing 100069，China

Research funding:

National Natural Science Foundation of China (81770611);

National Natural Science Foundation of China (82002243);

Key Projects of the Beijing Municipal Education Commission’s Science and Technology Plan (KZ202010025035);

Special Key Research Project of Capital Health Development Scientific Research (SF2020-1-1151);

Capital Clinical Characteristic Diagnosis and Treatment Technology Research and Transformation Application (Z191100006619096);

Capital Clinical Characteristic Diagnosis and Treatment Technology Research and Transformation Application (Z191100006619097);

Beijing Hospitals Authority Youth Programme (QML20201702);

Talent Cultivation Plan of “Climbing the peak” of Beijing Municipal Hospital Administration (DFL20221503);

High-level Public Health Technical Personnel Construction Project (Subject leaders-02-13);

Proposed Funding Project for the 2023 Beijing Natural Science Foundation Changping Innovation Joint Fund (L234046)

More Information

Corresponding author: REN Feng， renfeng7512@ccmu.edu.cn （ORCID： 0000-0001-7736-8637）
Received Date: 2023-12-28
Accepted Date: 2024-04-22
Published Date: 2024-09-25

Abstract

Abstract

Liver regeneration plays a crucial role in the recovery after liver injury induced by N-acetyl-p-aminophenol （APAP）. After APAP overdose， the degree of regeneration increases with the extent of liver injury， leading to the resolution of liver injury and spontaneous recovery in most cases. However， severe APAP overdose can impair liver regeneration and result in uncontrolled liver injury， even failure to recover or death in severe cases. Following APAP-induced liver injury， interactions between cells in the liver are essential for regenerative response. Liver regeneration is jointly regulated by multiple proliferative signaling pathways， involving various kinases， nuclear receptors， transcription factors， and coactivators. Severe APAP overdose can inhibit the activation of proliferative signaling pathways， thereby causing cell cycle arrest and impairing liver regeneration. Although liver regeneration plays a critical role in the repair of APAP-induced liver injury， the underlying mechanisms remain unclear. This article reviews the research advances in the role of liver regeneration in APAP-induced liver injury， in order to provide a reference for further basic research in this area.
- Chemical and Drug Induced Liver Injury,
- Acetaminophen,
- Signal Transduction,
- Repair

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References(36)

References

[1]	XU Y, XIA Y, LIU QH, et al. Glutaredoxin-1 alleviates acetaminophen-induced liver injury by decreasing its toxic metabolites[J]. J Pharm Anal, 2023, 13( 12): 1548- 1561. DOI: 10.1016/j.jpha.2023.08.004.
[2]	JAESCHKE H, RAMACHANDRAN A. Acetaminophen hepatotoxicity: Paradigm for understanding mechanisms of drug-induced liver injury[J]. Annu Rev Pathol, 2024, 19: 453- 478. DOI: 10.1146/annurev-pathmechdis-051122-094016.
[3]	RAMACHANDRAN A, AKAKPO JY, CURRY SC, et al. Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure[J]. Biochem Pharmacol, 2024: 116056. DOI: 10.1016/j.bcp.2024.116056.
[4]	APTE U, SINGH S, ZENG G, et al. Beta-catenin activation promotes liver regeneration after acetaminophen-induced injury[J]. Am J Pathol, 2009, 175( 3): 1056- 1065. DOI: 10.2353/ajpath.2009.080976.
[5]	NGUYEN NT, UMBAUGH DS, SANCHEZ-GUERRERO G, et al. Kupffer cells regulate liver recovery through induction of chemokine receptor CXCR2 on hepatocytes after acetaminophen overdose in mice[J]. Arch Toxicol, 2022, 96( 1): 305- 320. DOI: 10.1007/s00204-021-03183-0.
[6]	DONAHOWER B, MCCULLOUGH SS, KURTEN R, et al. Vascular endothelial growth factor and hepatocyte regeneration in acetaminophen toxicity[J]. Am J Physiol Gastrointest Liver Physiol, 2006, 291( 1): G102- G109. DOI: 10.1152/ajpgi.00575.2005.
[7]	BHUSHAN B, WALESKY C, MANLEY M, et al. Pro-regenerative signaling after acetaminophen-induced acute liver injury in mice identified using a novel incremental dose model[J]. Am J Pathol, 2014, 184( 11): 3013- 3025. DOI: 10.1016/j.ajpath.2014.07.019.
[8]	LUO TT, YANG SZ, ZHAO TM, et al. Hepatocyte DDX3X protects against drug-induced acute liver injury via controlling stress granule formation and oxidative stress[J]. Cell Death Dis, 2023, 14( 7): 400. DOI: 10.1038/s41419-023-05913-x.
[9]	MANGIPUDY RS, CHANDA S, MEHENDALE HM. Tissue repair response as a function of dose in thioacetamide hepatotoxicity[J]. Environ Health Perspect, 1995, 103( 3): 260- 267. DOI: 10.1289/ehp.95103260.
[10]	MICHALOPOULOS GK, BHUSHAN B. Liver regeneration: Biological and pathological mechanisms and implications[J]. Nat Rev Gastroenterol Hepatol, 2021, 18( 1): 40- 55. DOI: 10.1038/s41575-020-0342-4.
[11]	KOMPOSCH K, SIBILIA M. EGFR signaling in liver diseases[J]. Int J Mol Sci, 2015, 17( 1): 30. DOI: 10.3390/ijms17010030.
[12]	BHUSHAN B, KORAL K, STOOPS JW, et al. Hepatic deletion of MET aggravates acetaminophen hepatotoxicity and impairs liver regeneration in mice[J]. FASEB J, 2020, 34( S1): 1. DOI: 10.1096/fasebj.2020.34.s1.05879.
[13]	WEI MJ, GU XN, LI H, et al. EGR1 is crucial for the chlorogenic acid-provided promotion on liver regeneration and repair after APAP-induced liver injury[J]. Cell Biol Toxicol, 2023, 39( 6): 2685- 2707. DOI: 10.1007/s10565-023-09795-9.
[14]	KOTULKAR M, PAINE-CABRERA D, ABERNATHY S, et al. Role of HNF4alpha-cMyc interaction in liver regeneration and recovery after acetaminophen-induced acute liver injury[J]. Hepatology, 2023, 78( 4): 1106- 1117. DOI: 10.1097/HEP.0000000000000367.
[15]	BHUSHAN B, CHAVAN H, BORUDE P, et al. Dual role of epidermal growth factor receptor in liver injury and regeneration after acetaminophen overdose in mice[J]. Toxicol Sci, 2017, 155( 2): 363- 378. DOI: 10.1093/toxsci/kfw213.
[16]	ZHANG ZZ, YAO TT, ZHAO N, et al. Disruption of peroxisome proliferator-activated receptor α in hepatocytes protects against acetaminophen-induced liver injury by activating the IL-6/STAT3 pathway[J]. Int J Biol Sci, 2022, 18( 6): 2317- 2328. DOI: 10.7150/ijbs.69609.
[17]	SCHMIDT-ARRAS D, ROSE-JOHN S. IL-6 pathway in the liver: From physiopathology to therapy[J]. J Hepatol, 2016, 64( 6): 1403- 1415. DOI: 10.1016/j.jhep.2016.02.004.
[18]	CHIU H, GARDNER CR, DAMBACH DM, et al. Role of tumor necrosis factor receptor 1(p55) in hepatocyte proliferation during acetaminophen-induced toxicity in mice[J]. Toxicol Appl Pharmacol, 2003, 193( 2): 218- 227. DOI: 10.1016/j.taap.2003.07.003.
[19]	BHUSHAN B, POUDEL S, MANLEY MW Jr, et al. Inhibition of glycogen synthase kinase 3 accelerated liver regeneration after acetaminophen-induced hepatotoxicity in mice[J]. Am J Pathol, 2017, 187( 3): 543- 552. DOI: 10.1016/j.ajpath.2016.11.014.
[20]	POUDEL S, CABRERA DP, BHUSHAN B, et al. Hepatocyte-specific deletion of yes-associated protein improves recovery from acetaminophen-induced acute liver injury[J]. Toxicol Sci, 2021, 184( 2): 276- 285. DOI: 10.1093/toxsci/kfab115.
[21]	XU M, WANG HC, WANG JX, et al. mTORC2 signaling is necessary for timely liver regeneration after partial hepatectomy[J]. Am J Pathol, 2020, 190( 4): 817- 829. DOI: 10.1016/j.ajpath.2019.12.010.
[22]	MIREAULT M, PRINVILLE V, OHLUND L, et al. Semi-targeted profiling of bile acids by high-resolution mass spectrometry in a rat model of drug-induced liver injury[J]. Int J Mol Sci, 2023, 24( 3): 2489. DOI: 10.3390/ijms24032489.
[23]	EVERTON E, DEL RIO-MORENO M, VILLACORTA-MARTIN C, et al. Growth hormone accelerates recovery from acetaminophen-induced murine liver injury[J]. BioRxiv, 2023: 2023. 04. 17. 537197. DOI: 10.1101/2023.04.17.537197.
[24]	BORUDE P, BHUSHAN B, APTE U. DNA damage response regulates initiation of liver regeneration following acetaminophen overdose[J]. Gene Expr, 2018, 18( 2): 115- 123. DOI: 10.3727/105221618X15205260749346.
[25]	BIRD TG, MÜLLER M, BOULTER L, et al. TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence[J]. Sci Transl Med, 2018, 10( 454): eaan1230. DOI: 10.1126/scitranslmed.aan1230.
[26]	XU PF, XI Y, WANG PC, et al. Inhibition of p53 sulfoconjugation prevents oxidative hepatotoxicity and acute liver failure[J]. Gastroenterology, 2022, 162( 4): 1226- 1241. DOI: 10.1053/j.gastro.2021.12.260.
[27]	VISWANATHAN P, SHARMA Y, GUPTA P, et al. Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration[J]. Cell Prolif, 2018, 51( 3): e12445. DOI: 10.1111/cpr.12445.
[28]	MARTUCCI N, MICHALOPOULOS GK, MARS WM. Integrin linked kinase(ILK) and its role in liver pathobiology[J]. Gene Expr, 2021, 20( 3): 201- 207. DOI: 10.3727/105221621X16113475275710.
[29]	BHUSHAN B, EDWARDS G, DESAI A, et al. Liver-specific deletion of integrin-linked kinase in mice attenuates hepatotoxicity and improves liver regeneration after acetaminophen overdose[J]. Gene Expr, 2016, 17( 1): 35- 45. DOI: 10.3727/105221616X691578.
[30]	HU CX, ZHAO LF, WU ZW, et al. Transplantation of mesenchymal stem cells and their derivatives effectively promotes liver regeneration to attenuate acetaminophen-induced liver injury[J]. Stem Cell Res Ther, 2020, 11( 1): 88. DOI: 10.1186/s13287-020-01596-9.
[31]	CHANG WJ, SONG LJ, CHANG XJ, et al. Early activated hepatic stellate cell-derived paracrine molecules modulate acute liver injury and regeneration[J]. Lab Invest, 2017, 97( 3): 318- 328. DOI: 10.1038/labinvest.2016.130.
[32]	SHEN KT, CHANG WJ, GAO XD, et al. Depletion of activated hepatic stellate cell correlates with severe liver damage and abnormal liver regeneration in acetaminophen-induced liver injury[J]. Acta Biochim Biophys Sin, 2011, 43( 4): 307- 315. DOI: 10.1093/abbs/gmr005.
[33]	DONAHOWER BC, MCCULLOUGH SS, HENNINGS L, et al. Human recombinant vascular endothelial growth factor reduces necrosis and enhances hepatocyte regeneration in a mouse model of acetaminophen toxicity[J]. J Pharmacol Exp Ther, 2010, 334( 1): 33- 43. DOI: 10.1124/jpet.109.163840.
[34]	KATO T, ITO Y, HOSONO K, et al. Vascular endothelial growth factor receptor-1 signaling promotes liver repair through restoration of liver microvasculature after acetaminophen hepatotoxicity[J]. Toxicol Sci, 2011, 120( 1): 218- 229. DOI: 10.1093/toxsci/kfq366.
[35]	STARKEY LEWIS P, CAMPANA L, ALEKSIEVA N, et al. Alternatively activated macrophages promote resolution of necrosis following acute liver injury[J]. J Hepatol, 2020, 73( 2): 349- 360. DOI: 10.1016/j.jhep.2020.02.031.
[36]	BEN-MOSHE S, VEG T, MANCO R, et al. The spatiotemporal program of zonal liver regeneration following acute injury[J]. Cell Stem Cell, 2022, 29( 6): 973- 989. e 10. DOI: 10.1016/j.stem.2022.04.008.

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Role of liver regeneration in the repair of liver injury induced by N-acetyl-p-aminophenol

DOI: 10.12449/JCH240929

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Role of liver regeneration in the repair of liver injury induced by N-acetyl-p-aminophenol

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