Hepatic progenitor cells express SerpinB3

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• 作者：Gianmarco Villano (1)
  Cristian Turato (1)
  Santina Quarta (1)
  Mariagrazia Ruvoletto (1)
  Francesco Ciscato (1)
  Liliana Terrin (1)
  Rossella Semeraro (2)
  Claudia Paternostro (3)
  Maurizio Parola (3)
  Domenico Alvaro (2)
  Paolo Bernardi (4)
  Angelo Gatta (1)
  Patrizia Pontisso (1)
  
• 关键词：Hepatic progenitor cells ; C57BL/6J mouse ; SerpinB3 ; Mouse model ; LPS/D ; Galactosamine
• 刊名：BMC Cell Biology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：711 KB
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• 作者单位：Gianmarco Villano (1)
  Cristian Turato (1)
  Santina Quarta (1)
  Mariagrazia Ruvoletto (1)
  Francesco Ciscato (1)
  Liliana Terrin (1)
  Rossella Semeraro (2)
  Claudia Paternostro (3)
  Maurizio Parola (3)
  Domenico Alvaro (2)
  Paolo Bernardi (4)
  Angelo Gatta (1)
  Patrizia Pontisso (1)
  
  1. Department of Medicine-DIMED, University of Padua, Via Giustiniani 2, Padua, 35128, Italy
  2. Division of Gastroenterology, Department of Scienze e Biotecnologie Medico-Chirurgiche, Fondazione Eleonora Lorillard Spencer Cenci, University Sapienza, Rome, Viale dell’Università 37, Rome, 00185, Italy
  3. Department of Experimental Medicine and Oncology and Interuniversity Center for Liver Pathophysiology, University of Torino, Corso Raffaello 30, Torino, 10125, Italy
  4. Department of Biomedical Sciences, University of Padua, Viale Colombo 3, Padua, 35131, Italy
  
• ISSN：1471-2121

文摘

Background In the setting of liver injury hepatic progenitor cells are activated, counterbalancing the inhibited regenerative capacity of mature hepatocytes. Chronic activation of this compartment may give rise to a subset of liver tumours with poor prognosis. SerpinB3, a serpin over-expressed in injured liver and in primary liver cancer, has been shown to induce apoptosis resistance, epithelial to mesenchymal transition and to increase TGF-beta and Myc expression. Aim of the present study was to explore the presence of SerpinB3 in hepatic progenitor cells in human livers and in a mouse model of liver stem/progenitor cell activation. Hepatic progenitor cells were analysed in foetal and adult livers at protein and transcriptional levels. To induce experimental activation of the liver stem/progenitor compartment, C57BL/6J mice were injected with lipopolysaccharide plus D-galactosamine and were sacrificed at different time points. Liver cDNA was amplified using specific primers for mouse-homologous SerpinB3 isoforms and automatically sequenced. Results The presence of SerpinB3 in the progenitor cell compartment was detected in sorted human foetal and adult epithelial cell adhesion molecule (EpCAM) positive liver cells. By immunohistochemistry SerpinB3 was found in human cirrhotic livers in portal areas with progenitor cell activation showing ductular proliferation. CK-7, CK-19, EpCAM and CD-90 positive cell were also positive for SerpinB3. In the animal model, time course analysis in liver specimens revealed a progressive increase of SerpinB3 and a parallel decrease of activated caspase 3, which was barely detectable at 20?hours. Transcription analysis confirmed the presence of SerpinB3-homologous only in the liver of injured mice and sequence analysis proved its belonging to mouse Serpinb3b. Conclusion SerpinB3 is highly expressed in hepatic stem/progenitor cell compartment of both foetal and adult livers.