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Changes in E-NTPDase 3 expression and extracellular nucleotide hydrolysis during the myofibroblast/lipocyte differentiation

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Abstract

Hepatic stellate cells (HSC) play a critical role in the development and maintenance of liver fibrosis. HSC are lipocytes that displayed the capacity to develop into myofibroblast-like cells. Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) regulate the concentration of extracellular nucleotides, signaling molecules that play a role in the pathogenesis of hepatic fibrosis. In the present study, we identified and compared the expressions of E-NTPDase family members in two different phenotypes of the mouse hepatic stellate cell line (GRX) and evaluated the nucleotide hydrolysis by these cells. We show that both phenotypes of GRX cell line expressed NTPDase 3 and 5. However, only activated cells expressed NTPDase 6. In quiescent-like cells, the hydrolysis of triphosphonucleosides was significantly higher, and was related to an increase in Entpd3 mRNA expression. The diphosphonucleosides were hydrolyzed at a similar rate by two phenotypes of GRX cells. We suggest that up-regulation of Entpd3 mRNA expression modulates the extracellular concentration of nucleotides/nucleosides and affect P2-receptor signaling differently in quiescent-like cells and may play a role in the regulation of HSC functions.

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Acknowledgments

We thank Dr Carmem Gottfried for providing secondary goat anti-rabbit fluorescein conjugate. C. M. B. Andrade is recipient of a Ph.D. degree fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). A. M. O. Battastini, F. C. R. Guma, R. Borojevic, and R. Margis are recipients of research fellowships from CNPq. This study was supported by CNPq, FAPERJ, FAPERGS, and PROPESQ-UFRGS.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, 2600-anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Cláudia M. B. Andrade, Rogério Margis, Ana Maria O. Battastini & Fátima C. R. Guma

  2. Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, UFCSPA, Porto Alegre, RS, Brazil

    Márcia R. Wink

  3. Departamento de Histologia e Embriologia, ICB e PABCAM, Hospital Universitário Clementino Fraga Filho, UFRJ, Rio de Janeiro, RJ, Brazil

    Radovan Borojevic

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  1. Cláudia M. B. Andrade
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  2. Márcia R. Wink
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  3. Rogério Margis
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  5. Ana Maria O. Battastini
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  6. Fátima C. R. Guma
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Correspondence to Fátima C. R. Guma.

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Andrade, C.M.B., Wink, M.R., Margis, R. et al. Changes in E-NTPDase 3 expression and extracellular nucleotide hydrolysis during the myofibroblast/lipocyte differentiation. Mol Cell Biochem 339, 79–87 (2010). https://doi.org/10.1007/s11010-009-0371-3

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