Activity and expression of ecto-5'-nucleotidase/CD73 are increased during phenotype conversion of a hepatic stellate cell line.
Hepatic stellate cells (HSC) play a crucial role in the development of liver fibrosis and are important targets in liver disease therapy. Adenosine acts as an extracellular signaling molecule in various tissues and in liver this nucleoside exerts protective effects. Ecto-5'-nucleotidase/CD73 is a marker for the plasma membrane and is considered to be a key enzyme in the generation of adenosine in the extracellular medium, by transforming AMP into adenosine. In addition, adenosine production from AMP is also catalyzed by alkaline phosphatase. We compared the extracellular metabolism of AMP and transcriptional levels of the ecto-5'-nucleotidase/CD73 and tissue non-specific alkaline phosphatase (TNALP) in activated and quiescent HSC of the mouse hepatic stellate cell line GRX. This cell line expresses a myofibroblast phenotype in basal medium and both retinol and indomethacin treatment induced a phenotypic change of GRX cells to quiescent HSC. Ecto-5'-nucleotidase activity and its mRNA expression were found to be higher in quiescent HSC than in activated HSC. During phenotype conversion, mediated by retinol, the AMP decay was accelerated with adenosine accumulation in extracellular medium, likely due to the decrease in adenosine deaminase activity also observed in quiescent HSC. The treatment with retinol also involves transcriptional activation of TNALP. Taken together, these data suggest that ecto-5'-nucleotidase-dependent adenosine generation may play a role in the regulation of quiescent HSC functions.
Andrade
Cláudia M B
CM
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS. Porto Alegre, RS, Brazil.
Roesch
Gislaine C
GC
Wink
Márcia R
MR
Guimarães
Eduardo L M
EL
Souza
Luiz F
LF
Jardim
Fernanda Rafaela
FR
Guaragna
Regina M
RM
Bernard
Elena A
EA
Margis
Rogério
R
Borojevic
Radovan
R
Battastini
Ana Maria O
AM
Guma
Fátima C R
FC
D015720:5'-Nucleotidase / Q000096:biosynthesis / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D016922:Cellular Senescence; D004789:Enzyme Activation; D045604:Extracellular Fluid / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014801:Vitamin A / Q000494:pharmacology
D014801:Vitamin A; D000249:Adenosine Monophosphate; D000469:Alkaline Phosphatase; D015720:5'-Nucleotidase; D000241:Adenosine; D007213:Indomethacin