Hepatic progenitor cells express SerpinB3
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
BMC Cell Biology 2014, 15:5 doi:10.1186/1471-2121-15-5Published: 11 February 2014
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.
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.
SerpinB3 is highly expressed in hepatic stem/progenitor cell compartment of both foetal and adult livers.