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Hepatic progenitor cells express SerpinB3.

Villano G, Turato C, Quarta S, Ruvoletto M, Ciscato F, Terrin L, Semeraro R, Paternostro C, Parola M, Alvaro D, Bernardi P, Gatta A, Pontisso P - BMC Cell Biol. (2014)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine-DIMED, University of Padua, Via Giustiniani 2, Padua 35128, Italy. patrizia@unipd.it.

ABSTRACT

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.

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Immunohistochemistry in human liver cirrhosis. Immunohistochemistry on serial liver sections obtained from a cirrhotic patient with ductular proliferation. A) Representative images show negative control (C-) and immunostaining for cytokeratin 7 (CK-7), cytokeratin 19 (CK-19) and for SerpinB3. B) Serial liver sections immunostained for SerpinB3, EpCAM, CD-90, CD-34 and CD-117. Original magnification as indicated.
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Figure 1: Immunohistochemistry in human liver cirrhosis. Immunohistochemistry on serial liver sections obtained from a cirrhotic patient with ductular proliferation. A) Representative images show negative control (C-) and immunostaining for cytokeratin 7 (CK-7), cytokeratin 19 (CK-19) and for SerpinB3. B) Serial liver sections immunostained for SerpinB3, EpCAM, CD-90, CD-34 and CD-117. Original magnification as indicated.

Mentions: Immunohistochemistry was carried out in serial sections of human livers with HCV-related cirrhosis in order to evaluate the expression of SB3 in human progenitor cell compartment, typically found in portal tracts of cirrhotic livers as ductular reaction of CK-7 and CK-19 positive cells [4]. As shown in Figure 1A, staining of SB3 in consecutive liver sections clearly showed large numbers of CK-7 and CK-19 positive cells that also expressed SB3. In addition, similar areas positive for SB3 were also positive for EpCAM and CD-90, but negative for CD34 and for CD117 (Figure 1B), supporting the hypothesis that this serpin is expressed in this stem/progenitor cell compartment [18-22].


Hepatic progenitor cells express SerpinB3.

Villano G, Turato C, Quarta S, Ruvoletto M, Ciscato F, Terrin L, Semeraro R, Paternostro C, Parola M, Alvaro D, Bernardi P, Gatta A, Pontisso P - BMC Cell Biol. (2014)

Immunohistochemistry in human liver cirrhosis. Immunohistochemistry on serial liver sections obtained from a cirrhotic patient with ductular proliferation. A) Representative images show negative control (C-) and immunostaining for cytokeratin 7 (CK-7), cytokeratin 19 (CK-19) and for SerpinB3. B) Serial liver sections immunostained for SerpinB3, EpCAM, CD-90, CD-34 and CD-117. Original magnification as indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927218&req=5

Figure 1: Immunohistochemistry in human liver cirrhosis. Immunohistochemistry on serial liver sections obtained from a cirrhotic patient with ductular proliferation. A) Representative images show negative control (C-) and immunostaining for cytokeratin 7 (CK-7), cytokeratin 19 (CK-19) and for SerpinB3. B) Serial liver sections immunostained for SerpinB3, EpCAM, CD-90, CD-34 and CD-117. Original magnification as indicated.
Mentions: Immunohistochemistry was carried out in serial sections of human livers with HCV-related cirrhosis in order to evaluate the expression of SB3 in human progenitor cell compartment, typically found in portal tracts of cirrhotic livers as ductular reaction of CK-7 and CK-19 positive cells [4]. As shown in Figure 1A, staining of SB3 in consecutive liver sections clearly showed large numbers of CK-7 and CK-19 positive cells that also expressed SB3. In addition, similar areas positive for SB3 were also positive for EpCAM and CD-90, but negative for CD34 and for CD117 (Figure 1B), supporting the hypothesis that this serpin is expressed in this stem/progenitor cell compartment [18-22].

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine-DIMED, University of Padua, Via Giustiniani 2, Padua 35128, Italy. patrizia@unipd.it.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus