Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes

Hirohiko Ise, Nobuhiro Sugihara, Naoki Negishi, Toshio Nikaido, Toshihiro Akaike

Research output: Contribution to journalArticle

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Abstract

Development of a reliable method to isolate highly proliferative potential hepatocytes will provide insight into the molecular mechanisms of liver regeneration, as well as proving crucial for the development of a biohybrid artificial liver. The aim of this study is to isolate highly proliferative, e.g., progenitor-like, hepatocytes. To this end, we fractionated hepatocytes expressing low and high levels of the asialoglycoprotein receptor (ASGP-R) based on the difference in their adhesion to poly[N-p-vinylbenzyl-O-β-D-galactopyranosyl-(1→4)-D- gluconamide] (PVLA), and examined the proliferative activity and gene expression of these fractionated hepatocytes. The results showed that approximately 0.5 to 1% of the total number of hepatocytes, which showed low adhesion to PVLA, expressed low levels of the ASGP-R, while the rest of hepatocyte population with high adhesion to PVLA expressed high levels of the ASGP-R. Interestingly hepatocytes with low ASGP-R expression levels had much higher DNA synthesizing activity (i.e., are much more proliferative) than those with high ASGP-R expression levels. Moreover, hepatocytes with low ASGP-R expression levels expressed higher levels of epidermal growth factor receptor (EGF-R), CD29 (β1 integrin) and CD49f (α6 integrin) and lower levels of glutamine synthetase than those with high ASGP-R expression. These findings suggested that hepatocytes with low adhesion to PVLA due to their low ASGP-R expression could be potential candidates for progenitor-like hepatocytes due to their high proliferative capacity; hence, the low expression of the ASGP-R could be a unique marker for progenitor hepatocytes. The isolation of hepatocytes with different functional pheno-types using PVLA may provide a new research tool for a better understanding of the biology of hepatocytes and the mechanisms regulating their proliferation and differentiation in health and disease,

Original languageEnglish
Pages (from-to)172-182
Number of pages11
JournalBiochemical and Biophysical Research Communications
Volume285
Issue number2
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

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Asialoglycoprotein Receptor
Hepatocytes
Adhesion
Integrins
Liver
Artificial Liver
Glutamate-Ammonia Ligase
Liver Regeneration
Epidermal Growth Factor Receptor
Gene expression

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes. / Ise, Hirohiko; Sugihara, Nobuhiro; Negishi, Naoki; Nikaido, Toshio; Akaike, Toshihiro.

In: Biochemical and Biophysical Research Communications, Vol. 285, No. 2, 01.01.2001, p. 172-182.

Research output: Contribution to journalArticle

Ise, Hirohiko ; Sugihara, Nobuhiro ; Negishi, Naoki ; Nikaido, Toshio ; Akaike, Toshihiro. / Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 285, No. 2. pp. 172-182.
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abstract = "Development of a reliable method to isolate highly proliferative potential hepatocytes will provide insight into the molecular mechanisms of liver regeneration, as well as proving crucial for the development of a biohybrid artificial liver. The aim of this study is to isolate highly proliferative, e.g., progenitor-like, hepatocytes. To this end, we fractionated hepatocytes expressing low and high levels of the asialoglycoprotein receptor (ASGP-R) based on the difference in their adhesion to poly[N-p-vinylbenzyl-O-β-D-galactopyranosyl-(1→4)-D- gluconamide] (PVLA), and examined the proliferative activity and gene expression of these fractionated hepatocytes. The results showed that approximately 0.5 to 1{\%} of the total number of hepatocytes, which showed low adhesion to PVLA, expressed low levels of the ASGP-R, while the rest of hepatocyte population with high adhesion to PVLA expressed high levels of the ASGP-R. Interestingly hepatocytes with low ASGP-R expression levels had much higher DNA synthesizing activity (i.e., are much more proliferative) than those with high ASGP-R expression levels. Moreover, hepatocytes with low ASGP-R expression levels expressed higher levels of epidermal growth factor receptor (EGF-R), CD29 (β1 integrin) and CD49f (α6 integrin) and lower levels of glutamine synthetase than those with high ASGP-R expression. These findings suggested that hepatocytes with low adhesion to PVLA due to their low ASGP-R expression could be potential candidates for progenitor-like hepatocytes due to their high proliferative capacity; hence, the low expression of the ASGP-R could be a unique marker for progenitor hepatocytes. The isolation of hepatocytes with different functional pheno-types using PVLA may provide a new research tool for a better understanding of the biology of hepatocytes and the mechanisms regulating their proliferation and differentiation in health and disease,",
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