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The basis of liver regeneration: A systems biology approach.
Bhat, Mamatha; Pasini, Elisa; Baciu, Cristina; Angeli, Marc; Humar, Atul; Macparland, Sonya; Feld, Jordan; McGilvray, Ian.
Afiliação
  • Bhat M; Multi Organ Transplant Program, University Health Network, Toronto, Canada; Division of Gastroenterology and Hepatology, University Health Network and University of Toronto, Toronto, Canada. Electronic address: Mamatha.bhat@uhn.ca.
  • Pasini E; Multi Organ Transplant Program, University Health Network, Toronto, Canada.
  • Baciu C; Multi Organ Transplant Program, University Health Network, Toronto, Canada.
  • Angeli M; Multi Organ Transplant Program, University Health Network, Toronto, Canada.
  • Humar A; Multi Organ Transplant Program, University Health Network, Toronto, Canada.
  • Macparland S; Multi Organ Transplant Program, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, Toronto, Canada.
  • Feld J; Division of Gastroenterology and Hepatology, University Health Network and University of Toronto, Toronto, Canada; Toronto Centre for Liver Disease, University of Toronto, Ontario, Canada.
  • McGilvray I; Multi Organ Transplant Program, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, Toronto, Canada.
Ann Hepatol ; 18(3): 422-428, 2019.
Article em En | MEDLINE | ID: mdl-31047847
INTRODUCTION: Liver regeneration is a normal response to liver injury. The aim of this study was to determine the molecular basis of liver regeneration, through an integrative analysis of high-throughput gene expression datasets. METHODS: We identified and curated datasets pertaining to liver regeneration from the Gene Expression Omnibus, where regenerating liver tissue was compared to healthy liver samples. The key dysregulated genes and pathways were identified using Ingenuity Pathway Analysis software. There were three eligible datasets in total. RESULTS: In the early phase after hepatectomy, inflammatory pathways such as Nrf2 oxidative stress-mediated response and cytokine signaling were significantly upregulated. At peak regeneration, we discovered that cell cycle genes were predominantly expressed to promote cell proliferation. Using the Betweenness centrality algorithm, we discovered that Jun is the key central gene in liver regeneration. Calcineurin inhibitors may inhibit liver regeneration, based on predictive modeling. CONCLUSION: There is a paucity of human literature in defining the molecular mechanisms of liver regeneration along a time continuum. Nonetheless, using an integrative computational analysis approach to the available high-throughput data, we determine that the oxidative stress response and cytokine signaling are key early after hepatectomy, whereas cell cycle control is important at peak regeneration. The transcription factor Jun is central to liver regeneration and a potential therapeutic target. Future studies of regeneration in humans along a time continuum are needed to better define the underlying mechanisms, and ultimately enhance care of patients with acute and chronic liver failure while awaiting transplant.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Regulação da Expressão Gênica / Biologia de Sistemas / Hepatectomia / Regeneração Hepática Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Ann Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de publicação: México
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Regulação da Expressão Gênica / Biologia de Sistemas / Hepatectomia / Regeneração Hepática Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Ann Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2019 Tipo de documento: Article País de publicação: México