Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, 2600-anexo, Porto Alegre, RS CEP 90035-003, Brazil.
Mol Cell Biochem. 2010 Jun;339(1-2):79-87. doi: 10.1007/s11010-009-0371-3. Epub 2010 Jan 8.
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.
肝星状细胞 (HSC) 在肝纤维化的发生和维持中起着关键作用。HSC 是具有向肌成纤维细胞样细胞分化能力的脂肪细胞。细胞外核苷酸三磷酸二磷酸水解酶 (E-NTPDases) 调节细胞外核苷酸的浓度，核苷酸是参与肝纤维化发病机制的信号分子。在本研究中，我们鉴定并比较了两种不同表型的小鼠肝星状细胞系 (GRX) 中 E-NTPDase 家族成员的表达，并评估了这些细胞的核苷酸水解。结果显示，两种表型的 GRX 细胞系均表达 NTPDase 3 和 5。然而，只有活化细胞表达 NTPDase 6。在静止样细胞中，三磷酸核苷的水解率显著较高，与 Entpd3 mRNA 表达增加有关。两种表型的 GRX 细胞以相似的速率水解二磷酸核苷。我们认为，Entpd3 mRNA 表达的上调调节了细胞外核苷酸/核苷的浓度，并以不同的方式影响静止样细胞中 P2 受体信号，可能在调节 HSC 功能中发挥作用。
