[Inhibition of S1PR2 activity down-regulates expressions of sphingosine kinase 1 and MCP-1 in rat glomerular mesangial cells under high glucose].

OBJECTIVE:To investigate the effects of high glucose and the specific antagonist JTE-013 of sphingosine-1-phosphate receptor 2 (S1PR2) on the expressions of sphingosine kinase 1 (Sphk1), S1PR2 and monocyte chemoattractant protein-1 (MCP-1) in rat glomerular mesangial cells. METHODS:The cultured rat GMCs were divided into four groups: normal glucose control group (NG, with 5.5 mmol/L glucose), mannitol group (HM, with 5.5 mmol/L glucose and 24.5 mmol/L mannitol), high glucose group (HG, with 30 mmol/L glucose), JTE-013 group (HJ, with 30 mmol/L glucose and 10 μmol/L JTE-013). The mRNA levels of SphK1, S1PR2 and MCP-1 were determined with real-time quantitative PCR in the cells at 0, 12, 24 and 48 hours, respectively, and the protein expression of MCP-1 in the supernatant was determined with ELISA . RESULTS:Compared with those in normal glucose, the mRNAs of SphK1 and S1PR2 in rat GMCs under high glucose were down-regulated at 12 hours and were then up-regulated as time went on, and peaked at 48 hours. High glucose significantly enhanced the mRNA expression of MCP-1 at 12 hours, and the expression reached the highest levels at 24 hours, but decreased at 48 hours. The protein expression of MCP-1 in rat GMCs time-dependently increased under high glucose compared with that in NG. After GMCs were treated with 10 μmol/L JTE-013 before exposed to high glucose for 24 hours, the mRNA levels of SphK1, S1PR2 and MCP-1 and the protein expression of MCP-1 significantly decreased compared with those in HG. CONCLUSION:Inhibition of S1PR2 activity could down-regulate the expressions of SphK1 and MCP-1 in rat GMCs under high glucose.

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