title: [MicroRNA-210 mediates the protective effect of rosuvastatin on human mesenchymal stem cells apoptosis induced by tumor necrosis factor-α].
abstract: OBJECTIVE
  To explore the effect and mechanism of rosuvastatin on tumor necrosis factor-α induced human mesenchymal stem cells (MSCs) apoptosis.
  
  
  METHODS
  Human MSCs were treated as follows: (1) culture medium; (2) TNF-α (20 µg/ml) for 6 h; (3) rosuvastatin (20 µmol/L) for 24 h; (4) rosuvastatin (20 µmol/L) for 24 h followed by TNF-α (20 µg/ml) for 6 h; (5) TNF-α+rosuvastatin+50 nmol/L antago-miRNA; (6) TNF-α+rosuvastatin+100 nmol/L antago-miRNA. Cell survival and apoptosis were determined by MTT, TUNEL and caspase-3 activity assay. The changes of miRNA-210 in each group were detected with quantitative PCR.
  
  
  RESULTS
  TNF-α significantly induced human MSCs apoptosis in a concentration-dependent manner, and pretreatment with rosuvastatin significantly reduced MSCs apoptosis (caspase-3 assay: TNF-α+Statin group vs. TNF-α group: (1.63 ± 0.25) vs. (2.05 ± 0.36), P < 0.05). Meanwhile, TNF-α progressively reduced the expression of miRNA-210 in human MSCs in a dose-dependent manner, while the miRNA-210 expression was significantly upregulated in TNF-α+Statin group (P < 0.05). The protective effect of rosuvastatin on TNF-α induced MSCs apoptosis was largely abolished by co-treatment with 100 nmol/L antago-miRNA (TUNEL:TNF-α + Statin + antago-miR group vs. TNF-α + Statin group: (42.58 ± 6.71) % vs. (16.87 ± 9.27) %, P < 0.05).
  
  
  CONCLUSIONS
  Pretreatment with rosuvastatin can significantly improve the viability of human MSCs after TNF-α injury, the protective mechanism of rosuvastatin is partly mediated through miRNA-210 up-regulation.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
authors.forename: Daoyuan
authors.initials: D
authors.lastname: Ren
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Fu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
authors.forename: Sishi
authors.initials: S
authors.lastname: Cai
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China. Email: qian.juying@zs-hospital.sh.cn.
authors.forename: Juying
authors.initials: J
authors.lastname: Qian
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D002470:Cell Survival; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D035683:MicroRNAs / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D011743:Pyrimidines; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000068718:Rosuvastatin Calcium; D053148:Caspase 3