Activity and expression of ecto-5′-nucleotidase/CD73 are increased during phenotype conversion of a hepatic stellate cell line

Andrade, Claudia Marlise Balbinotti; Roesch, Gislaine C.; Guimarães, Eduardo Linck Machado; Souza, Luiz Carlos Bento de; Jardim, Fernanda Rafaela; Guaragna, Regina Maria Vieira da Costa; Bernard, Elena Aida; Margis, Rogério; Borojević, Radovan; Battastini, Ana Maria Oliveira; Guma, Fátima Costa Rodrigues

doi:10.1016/j.lfs.2007.10.003

Cited by 23 publications

(20 citation statements)

References 50 publications

(50 reference statements)

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“…Liver fibrosis is an exceedingly complex pathophysiological syndrome (Bataller and Brenner, 2005). Some findings suggest that adenosine and adenosine receptors function as profibrotic signal in liver fibrosis Peng et al, 2008), whereas others indicate a protective role of adenosine in the process of fibrogenesis (Herná ndez-Muñ oz et al, 1997; Hashmi et al, 2007;Andrade et al, 2008). Our studies extended those observations by elucidating a contradictory role of A 1 AR in the pathogenesis of liver fibrosis.…”

Section: Discussionsupporting

confidence: 69%

A Contradictory Role of A₁ Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice

Yang

Han²,

Chen³

et al. 2009

J Pharmacol Exp Ther

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Section: Discussionsupporting

confidence: 69%

A Contradictory Role of A₁ Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice

Yang

Han²,

Chen³

et al. 2009

J Pharmacol Exp Ther

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“…Thus, it is presently unclear, whether intact endothelial cell CD73 activity is increased as suggested from cell membrane preparations or decreased in response to DHA treatment due to more complex regulatory events on the cellular level. Furthermore, alkaline phosphatase, which hydrolyses extracellular adenine nucleotides in parallel to CD73, should be included in a comprehensive analysis of adenine nucleotide metabolism [17]. …”

Section: Introductionmentioning

confidence: 99%

Regulation of Ecto-5´-Nucleotidase by Docosahexaenoic Acid in Human Endothelial Cells

Thom¹,

Wendel²,

Deußen³

2013

Cell Physiol Biochem

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Background/Aims: Modulation of extracellular adenine nucleotide and adenosine concentrations is one potential mechanism by which docosahexaenoic acid (DHA) may exert beneficial effects in critically ill patients. This study assessed DHA effects on extracellular adenine purines. Methods: Experiments used human pulmonary endothelial cells (HPMEC) and umbilical vein endothelial cells (HUVEC) treated with DHA (48 h). mRNA level (real-time PCR), expression (western blot, flow cytometry) and activities (hydrolysis of etheno(ε)-purines and fluorescence HPLC) of CD73 (ecto-5´-nucleotidase) and CD39 (ecto-NTPDase-1) were quantified. Results: DHA elevated total CD73 membrane protein expression concentration-dependently but CD73 mRNA level did not change. Increased expression was paralleled by increased enzyme activity. Effects observed on membrane level were reversed in intact cells, in which ε-AMP hydrolysis decreased after DHA. In intact endothelial cells ATP release was enhanced and CD39 activity blunted following DHA treatment. Hence, extracellular ATP and ADP concentrations increased and this inhibited ε-AMP hydrolysis. Conclusion: In human endothelial cells DHA caused 1) up-regulation of CD73 protein content and increased AMP hydrolysis at the cell membrane level, 2) increased cellular ATP release, and 3) decreased extracellular ATP/ADP hydrolysis. Thus, reorganization of the extracellular adenine-nucleotide-adenosine axis in response to DHA resulted in an increased extracellular ATP/adenosine ratio.

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“…Subsequently, canalicular bile flows into the lumen of an extensive network of intrahepatic ducts, where it undergoes dilution and alkalinisation as a result of cholangiocyte Cl -and HCO 3 -secretion. P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 and P2X4 receptor mRNA was identified in isolated, microperfused IBDUs using RT-PCR [69]. cAMP-induced secretion of bicarbonate from IBDUs involves apical release of ATP and stimulation of apical P2 receptors [180].…”

Section: Bile Canaliculi and Hepatic Coupletsmentioning

confidence: 99%

“…NTPDase2 is a preferential ATPase that appears to have major effects in inflammation and biliary type fibrogenesis that are related to generation of ADP. Ecto-5′-nucleotidase (CD73) activity was found to be higher in the quiescent, rather than in the activated phenotype of a HSC line, suggesting that ecto-5′-nucleotidase-dependent adenosine production may play a role in the regulation of quiescent HSC functions [6]. However, it has been claimed recently that ecto-5′-nucleotidase (CD73) gene expression increased in both HSC and portal fibroblasts during myofibroblastic differentiation and represents a promising target for antifibrotic therapy [85].…”

Section: Fibrosis and Hscsmentioning

confidence: 99%

“…Nucleotide receptors were separated into P2X ligand-gated ion channel and P2Y G protein-coupled receptors [206]. Currently, four subtypes of P1 receptors (A 1 , A 2A , A 2B and A 3 ), seven subtypes of P2X (P2X1-7) and eight subtypes of P2Y receptors (P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 12 , P2Y 13 and P2Y 14 ) are recognised [34]. ATP is established as a cotransmitter with classical transmitters in most, if not all, nerves in the peripheral and central nervous systems (see [35]), and receptors are expressed on many non-neuronal, as well as neuronal cell types (see [36]).…”

Section: Introductionmentioning

confidence: 99%

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Purinergic signalling in the liver in health and disease

Burnstock

Vaughn

Robson

2013

Purinergic Signalling

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Purinergic signalling is involved in both the physiology and pathophysiology of the liver. Hepatocytes, Kupffer cells, vascular endothelial cells and smooth muscle cells, stellate cells and cholangiocytes all express purinoceptor subtypes activated by adenosine, adenosine 5′-triphosphate, adenosine diphosphate, uridine 5′-triphosphate or UDP. Purinoceptors mediate bile secretion, glycogen and lipid metabolism and indirectly release of insulin. Mechanical stress results in release of ATP from hepatocytes and Kupffer cells and ATP is also released as a cotransmitter with noradrenaline from sympathetic nerves supplying the liver. Ectonucleotidases play important roles in the signalling process. Changes in purinergic signalling occur in vascular injury, inflammation, insulin resistance, hepatic fibrosis, cirrhosis, diabetes, hepatitis, liver regeneration following injury or transplantation and cancer. Purinergic therapeutic strategies for the treatment of these pathologies are being explored.

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Activity and expression of ecto-5′-nucleotidase/CD73 are increased during phenotype conversion of a hepatic stellate cell line

Cited by 23 publications

References 50 publications

A Contradictory Role of A₁ Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice

A Contradictory Role of A₁ Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice

Regulation of Ecto-5´-Nucleotidase by Docosahexaenoic Acid in Human Endothelial Cells

Purinergic signalling in the liver in health and disease

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Activity and expression of ecto-5′-nucleotidase/CD73 are increased during phenotype conversion of a hepatic stellate cell line

Cited by 23 publications

References 50 publications

A Contradictory Role of A1 Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice

A Contradictory Role of A1 Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice

Regulation of Ecto-5´-Nucleotidase by Docosahexaenoic Acid in Human Endothelial Cells

Purinergic signalling in the liver in health and disease

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Product

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A Contradictory Role of A₁ Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice

A Contradictory Role of A₁ Adenosine Receptor in Carbon Tetrachloride- and Bile Duct Ligation-Induced Liver Fibrosis in Mice