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Publication : Cloning of the rat ADAMTS-1 gene and its down regulation in endothelial cells in cirrhotic rats.

First Author  Diamantis I Year  2000
Journal  Liver Volume  20
Issue  2 Pages  165-72
PubMed ID  10847486 Mgi Jnum  J:63549
Mgi Id  MGI:1861164 Doi  10.1034/j.1600-0676.2000.020002165.x
Citation  Diamantis I, et al. (2000) Cloning of the rat ADAMTS-1 gene and its down regulation in endothelial cells in cirrhotic rats. Liver 20(2):165-72
abstractText  AIMS: This study was undertaken in order to identify genes which are regulated during the process of liver fibrosis. METHODS: The differential display method and RNA from rat endothelial cells before and after induction of cirrhosis were used. RESULTS: A 496 bp fragment, which was down regulated in liver endothelial cells from a cirrhotic animal, was cloned. The cloned fragment showed a 95% homology with the newly cloned mouse ADAMTS-1 gene (a disintegrin and metalloproteinase with thrombospondin motifs), which is implicated in inflammation. The fragment was found to span the 3' of exon 6, the whole exon 7 and the 5' of exon 8. Sequencing of the entire coding region of the rat gene showed a 94% homology at the nucleic acid level and 96% homology at the amino acid level. The sequences responsible for the function of the protein were conserved. Northern blot analysis, using the cloned fragment as a probe, confirmed the finding that the gene was down-regulated in endothelial cells derived from livers of cirrhotic animals. In situ PCR analysis localised the ADAMTS-1 gene in the liver endothelial cells from normal animals. CONCLUSIONS: Regulation of the expression of genes which belong to the metalloproteinase family in liver endothelial cells might be important in the development of liver cirrhosis.
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