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Comparison of liver regeneration after partial hepatectomy and acetaminophen-induced acute liver failure: A global picture based on transcriptome analysis.
Bhushan, Bharat; Gunewardena, Sumedha; Edwards, Genea; Apte, Udayan.
Afiliação
  • Bhushan B; Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Gunewardena S; Department of Molecular and Integrative Physiology, Kansas City, KS, USA.
  • Edwards G; Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
  • Apte U; Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: uapte@kumc.edu.
Food Chem Toxicol ; 139: 111186, 2020 May.
Article em En | MEDLINE | ID: mdl-32045647
Liver regenerates following surgical removal and after drug-induced liver injury (DILI). However, most of the mechanisms of liver regeneration were identified using partial hepatectomy (PHX) model rather than using DILI models. We compared mechanisms of liver regeneration following PHX and after acetaminophen (APAP) overdose, a DILI model, using transcriptomic approach. Kinetics of hepatocyte proliferation and global gene expression profiles were studied in male C57BL/6J mice either subjected to PHX or following APAP overdose. Liver regeneration was much more synchronized after PHX as compared to APAP overdose. Transcriptomics analysis revealed activation of common upstream regulators in both models including growth factors HGF, EGF and VEGF; and cytokines IL6 and TNFα. However, magnitude of activation and temporality was significantly differed between the two models. HGF and VEGF showed similar activation between PHX and APAP but activation of EGF was significantly stronger in the APAP model. Activation of IL6 and TNFα transcriptional programs was delayed but remarkably higher in APAP. These dissimilarities could be attributed to inherent differences in the two models including significant injury and inflammation exclusively in the APAP model. This study highlights need to study mechanisms of liver regeneration after DILI separately from the mechanisms of regeneration PHX.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Falência Hepática Aguda / Perfilação da Expressão Gênica / Hepatectomia / Regeneração Hepática / Acetaminofen Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Food Chem Toxicol Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Falência Hepática Aguda / Perfilação da Expressão Gênica / Hepatectomia / Regeneração Hepática / Acetaminofen Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Food Chem Toxicol Ano de publicação: 2020 Tipo de documento: Article