Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression
BACKGROUND: Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation...
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Sociedad de Biología de Chile
2015
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oai:scielo:S0716-976020150001000452016-02-16Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expressionLee,SeahyoungYun,InaHam,OnjuLee,Se-YeonLee,Chang YeonPark,Jun-HeeLee,JiyunSeo,Hyang-HeeChoi,EunhyunHwang,Ki-Chul Hexokinase II miRNA-181a Cell death Mesenchymal stem cell BACKGROUND: Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated. RESULTS: H2O2 (600 μΜ) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2. CONCLUSIONS: These findings suggest that H2O2-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.48 20152015-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100045en10.1186/S40659-015-0036-5 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
Hexokinase II miRNA-181a Cell death Mesenchymal stem cell |
| spellingShingle |
Hexokinase II miRNA-181a Cell death Mesenchymal stem cell Lee,Seahyoung Yun,Ina Ham,Onju Lee,Se-Yeon Lee,Chang Yeon Park,Jun-Hee Lee,Jiyun Seo,Hyang-Hee Choi,Eunhyun Hwang,Ki-Chul Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression |
| description |
BACKGROUND: Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated. RESULTS: H2O2 (600 μΜ) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2. CONCLUSIONS: These findings suggest that H2O2-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues. |
| author |
Lee,Seahyoung Yun,Ina Ham,Onju Lee,Se-Yeon Lee,Chang Yeon Park,Jun-Hee Lee,Jiyun Seo,Hyang-Hee Choi,Eunhyun Hwang,Ki-Chul |
| author_facet |
Lee,Seahyoung Yun,Ina Ham,Onju Lee,Se-Yeon Lee,Chang Yeon Park,Jun-Hee Lee,Jiyun Seo,Hyang-Hee Choi,Eunhyun Hwang,Ki-Chul |
| author_sort |
Lee,Seahyoung |
| title |
Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression |
| title_short |
Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression |
| title_full |
Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression |
| title_fullStr |
Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression |
| title_full_unstemmed |
Suppression of miR-181 a attenuates H2O2-induced death of mesenchymal stem cells by maintaining hexokinase II expression |
| title_sort |
suppression of mir-181 a attenuates h2o2-induced death of mesenchymal stem cells by maintaining hexokinase ii expression |
| publisher |
Sociedad de Biología de Chile |
| publishDate |
2015 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100045 |
| work_keys_str_mv |
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| _version_ |
1718441538917236736 |