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Fibronectin and laminin induce expression of islet cell markers in hepatic oval cells in culture

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Abstract

Hepatic oval cells (OC) are considered to be facultative liver stem cells and, because they may undergo differentiation into a variety of cell lineages, they might have the potential to be used in cellular therapy. Signals delivered by extracellular matrix (ECM) proteins take part in cellular differentiation in cooperation with signals from growth factors; indeed, some ECM proteins, such as laminin (LAM) and fibronectin (FN), have been shown to contribute to β-cell differentiation and islet development, respectively. Since no previous studies have investigated the effect of ECM proteins on the expression of islet cell markers by cultured OC, the purpose of the present study was to evaluate whether FN and LAM modulate the expression of genes related to the endocrine pancreas in these liver cells. OC proliferation was induced in Wistar rats by prolonged treatment with 2-acetoaminofluorene/allyl alcohol and confirmed by reverse transcription/polymerase chain reaction and hepatic immunocytochemical and histopathological analyses. OC isolation was performed by Ficoll gradient and magnetic-activated cell sorting. OC were cultured for 1 and 2 months under several conditions with specific growth factors, over a FN or LAM substrate or in high glucose, nicotinamide and fetal calf serum. OC cultured on FN substrate expressed Pdx-1, Pax-6, insulin 2 and glucagon. LAM also induced the expression of Pdx-1, insulin 1 and insulin 2, glucagon, somatostatin and GLUT-2. Our results suggest that these ECM proteins can be used in protocols of OC transdifferentiation aimed at reducing the period necessary for complete transdifferentiation.

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Acknowledgments

We are greatful to Verônica Gonçalvez and Edith Amaral for performing the immunocytochemical analysis.

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Authors and Affiliations

  1. Laboratory for Cellular and Molecular Endocrinology (LIM-25), University of São Paulo School of Medicine, Av. Dr. Arnaldo, 455 s/4307, 01246-903, São Paulo, Brazil

    Adriana Ribeiro Leite, Maria Lúcia Corrêa-Giannella, Maria Angela Zanela Fortes, Vanina Monique Tucci Vegas & Daniel Giannella-Neto

  2. Institute of Veterinary Medicine, University of São Paulo, São Paulo, Brazil

    Maria Lúcia Zaidan Dagli

Authors
  1. Adriana Ribeiro Leite
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  2. Maria Lúcia Corrêa-Giannella
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  3. Maria Lúcia Zaidan Dagli
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  4. Maria Angela Zanela Fortes
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  5. Vanina Monique Tucci Vegas
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  6. Daniel Giannella-Neto
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Correspondence to Daniel Giannella-Neto.

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This study was supported by FAPESP (Process number 02/13098-4), São Paulo, Brazil.

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Leite, A.R., Corrêa-Giannella, M.L., Dagli, M.L.Z. et al. Fibronectin and laminin induce expression of islet cell markers in hepatic oval cells in culture. Cell Tissue Res 327, 529–537 (2007). https://doi.org/10.1007/s00441-006-0340-z

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  • DOI: https://doi.org/10.1007/s00441-006-0340-z

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