MicroRNA-210 mediates the protective effect of rosuvastatin on human mesenchymal stem cells apoptosis induced by tumor necrosis factor-α.
- Author:
Jianfeng XU
1
;
Daoyuan REN
1
;
Mingqiang FU
1
;
Yanhua GAO
1
;
Yi LOU
1
;
Sishi CAI
1
;
Juying QIAN
2
;
Junbo GE
1
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Caspase 3; Cell Survival; Fluorobenzenes; pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mesenchymal Stromal Cells; drug effects; MicroRNAs; pharmacology; Pyrimidines; pharmacology; Rosuvastatin Calcium; Sulfonamides; pharmacology; Tumor Necrosis Factor-alpha; drug effects; Up-Regulation
- From: Chinese Journal of Cardiology 2014;42(11):932-937
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the effect and mechanism of rosuvastatin on tumor necrosis factor-α induced human mesenchymal stem cells (MSCs) apoptosis.
METHODHuman 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.
RESULTTNF-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).
CONCLUSIONPretreatment 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.
