title: [Inhibition of S1PR2 activity down-regulates expressions of sphingosine kinase 1 and MCP-1 in rat glomerular mesangial cells under high glucose].
abstract: 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.
  
  
  CONCLUSIONS
  Inhibition of S1PR2 activity could down-regulate the expressions of SphK1 and MCP-1 in rat GMCs under high glucose.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Can
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D050527:Mesangial Cells / Q000201:enzymology / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase
chemical_list: D018932:Chemokine CCL2; D005947:Glucose; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase; C491766:Ccl2 protein, rat; C570053:sphingosine-1-phosphate receptor-2, rat