PMID- 25575056 OWN - NLM STAT- MEDLINE DCOM- 20150817 LR - 20191210 IS - 1007-8738 (Print) IS - 1007-8738 (Linking) VI - 31 IP - 1 DP - 2015 Jan TI - [Inhibition of S1PR2 activity down-regulates expressions of sphingosine kinase 1 and MCP-1 in rat glomerular mesangial cells under high glucose]. PG - 36-9 AB - 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 mumol/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 mumol/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. FAU - Lei, Sha AU - Lei S AD - Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. FAU - Wang, Qiuyue AU - Wang Q AD - Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. FAU - Lv, Chuan AU - Lv C AD - Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. FAU - Wu, Can AU - Wu C AD - Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. FAU - Yuan, Qin AU - Yuan Q AD - Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. FAU - Han, Jinyu AU - Han J AD - Department of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. LA - chi PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi JT - Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology JID - 101139110 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, Lysosphingolipid) RN - 0 (Sphingosine-1-Phosphate Receptors) RN - 0 (sphingosine-1-phosphate receptor-2, rat) RN - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)) RN - EC 2.7.1.- (sphingosine kinase) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Chemokine CCL2/genetics/*metabolism MH - Diabetic Nephropathies/enzymology/genetics/*metabolism MH - *Down-Regulation MH - Glucose/*metabolism MH - Humans MH - Mesangial Cells/enzymology/*metabolism MH - Phosphotransferases (Alcohol Group Acceptor)/genetics/*metabolism MH - Rats MH - Receptors, Lysosphingolipid/genetics/*metabolism MH - Sphingosine-1-Phosphate Receptors EDAT- 2015/01/13 06:00 MHDA- 2015/08/19 06:00 CRDT- 2015/01/10 06:00 PHST- 2015/01/10 06:00 [entrez] PHST- 2015/01/13 06:00 [pubmed] PHST- 2015/08/19 06:00 [medline] PST - ppublish SO - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 Jan;31(1):36-9.