Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to elucidate the morphometric changes occurring in hepatic lymphatics in human chronic viral liver diseases and to investigate the relationship between liver fibrosis, liver inflammation, and these changes. The lymphatic vessels were stained intensely by enzyme histochemistry for 5'-nucleotidase, whereas blood vessels stained well for alkaline phosphatase. We performed a morphometric analysis to estimate the number of lymphatic and blood vessels and their areas, using computer graphics software (NIH Image). Both the number of lymphatics in the specimens and their areas were increased according to the degree of liver fibrosis, but neither showed any relationship with the degree of activity of hepatitis. Neither the number nor the areas of the blood vessels showed any obvious relationship with the degree of fibrosis or the activity of chronic hepatitis. Correlation between clinical and laboratory data and the sizes and number of the lymphatics supported these morphological data. Our results clarified that the sizes and number of lymphatics are related to the stage of fibrosis in chronic viral liver diseases. This is thought to be due to increased lymph production, which is caused by the disturbance of the microcirculation associated with liver fibrosis.
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PMID:Morphometric analysis of lymphatic and blood vessels in human chronic viral liver diseases. 977 44

Ecto-5'-nucleotidase (eNT/CD73, E.C.3.1.3.5) is a glycosyl phosphatidylinositol (GPI)-linked cell-surface protein with several functions, including the local generation of adenosine from AMP, with the consequent activation of adenosine receptors and the salvaging of extracellular nucleotides. It also apparently functions independently of this activity, e.g., in the mediation of cell-cell adhesion. Liver fibrosis can be considered as a dynamic and integrated cellular response to chronic liver injury and the activation of hepatic stellate cells (HSCs) plays a role in the fibrogenic process. eNT/CD73 and adenosine are reported to play an important role in hepatic fibrosis in murine models. Knockdown of eNT/CD73 leads to an increase in mRNA expression of tissue non-specific alkaline phosphatase (TNALP), another AMP-degrading enzyme and thus no alteration is seen in the total ecto-AMPase activity of the cell. eNT/CD73 knockdown also leads to changes in the expression of collagen I and a clear alteration of cell migration. We suggest that eNT/CD73 protein expression controls cell migration and collagen expression in a mechanism independent of changes in nucleotide metabolism.
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PMID:Ecto-5'-nucleotidase/CD73 knockdown increases cell migration and mRNA level of collagen I in a hepatic stellate cell line. 2142 67

Adenosine is a potent modulator of liver fibrosis and inflammation. Adenosine has been shown to regulate such diverse activities as chemotaxis, contraction, and matrix production in hepatic stellate cells (HSC). Ecto-5'-nucleotidase/CD73 [EC 3.1.3.5] is the rate-limiting enzyme in adenosine production. Cd73-deficient mice are resistant to experimental liver fibrosis and have impaired adenosine generation. However, cell-specific expression and regulation of CD73 within the fibrotic liver have not been defined. In particular, prior evidence demonstrating that liver myofibroblasts, the cells believed to be responsible for matrix formation in the liver, express CD73 is lacking. Thus we tested the hypothesis that HSC and portal fibroblasts (PF), cells that undergo differentiation into liver myofibroblasts, express CD73 in a regulated fashion. We found that CD73 is weakly expressed in quiescent HSC and PF but is markedly upregulated at the transcriptional level in myofibroblastic HSC and PF. We furthermore found that CD73 protein and its functional activity are strongly increased in fibrous septa in rats subjected to experimental fibrosis. To determine the mechanism for the upregulation of Cd73 gene, we cloned the rat Cd73 promoter and then used serial truncation and site-directed mutagenesis to identify key regulatory elements. We identified two consensus SP1 motifs and one SMAD binding site, each of which was necessary for Cd73 gene upregulation. In conclusion, activated HSC upregulate Cd73 gene expression, via specific SP1 and SMAD promoter elements, after myofibroblastic differentiation. The ecto-5'-nucleotidase/CD73 enzyme is a novel cellular marker of activated liver myofibroblasts in vivo and in vitro and thus represents a promising molecular target for antifibrotic therapies in liver diseases.
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PMID:Activated hepatic stellate cells upregulate transcription of ecto-5'-nucleotidase/CD73 via specific SP1 and SMAD promoter elements. 2289 23