Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p.
<h4>Background</h4>Luteolin (LUT), a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R). Howev...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144877&type=printable |
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| author | Chen Bian Tongda Xu Hong Zhu Defeng Pan Yang Liu Yuanyuan Luo Pei Wu Dongye Li |
| author_facet | Chen Bian Tongda Xu Hong Zhu Defeng Pan Yang Liu Yuanyuan Luo Pei Wu Dongye Li |
| author_sort | Chen Bian |
| collection | DOAJ |
| description | <h4>Background</h4>Luteolin (LUT), a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R). However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs). The purpose of this study was to determine which miRs and target genes LUT exerted such function through.<h4>Methods</h4>Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets) oncogene homolog 1). MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3'-untranslated region of Ets1.<h4>Results</h4>LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.<h4>Conclusion</h4>LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels. |
| format | Article |
| id | doaj-art-0cc2e51c47b045d68d683019d5e954f6 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-0cc2e51c47b045d68d683019d5e954f62025-08-20T02:15:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014487710.1371/journal.pone.0144877Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p.Chen BianTongda XuHong ZhuDefeng PanYang LiuYuanyuan LuoPei WuDongye Li<h4>Background</h4>Luteolin (LUT), a kind of flavonoid which is extracted from a variety of diets, has been reported to convey protective effects of various diseases. Recent researches have suggested that LUT can carry out cardioprotective effects during ischemia/reperfusion (I/R). However, there have no reports on whether LUT can exert protective effects against myocardial I/R injury through the actions of specific microRNAs (miRs). The purpose of this study was to determine which miRs and target genes LUT exerted such function through.<h4>Methods</h4>Expression of various miRs in perfused rat hearts was detected using a gene chip. Target genes were predicted with TargetScan, MiRDB and MiRanda. Anoxia/reoxygenation was used to simulate I/R. Cells were transfected by miR-208b-3p mimic, inhibitor and small interfering RNA of Ets1 (avian erythroblastosis virus E26 (v ets) oncogene homolog 1). MiR-208b-3p and Ets1 mRNA were quantified by real-time quantitative polymerase chain reaction. The percentage of apoptotic cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide dyeing and flow cytometry. The protein expression levels of cleaved caspase-3, Bcl-2, Bax, and Ets1 were examined by western blot analysis. A luciferase reporter assay was used to verify the combination between miR-208b-3p and the 3'-untranslated region of Ets1.<h4>Results</h4>LUT pretreatment reduced miR-208b-3p expression in myocardial tissue, as compared to the I/R group. And LUT decreased miR-208b-3p expression and apoptosis caused by I/R. However, overexpression of miR-208b-3p further aggravated the changes caused by I/R and blocked all the effects of LUT. Knockdown of miR-208b-3p expression also attenuated apoptosis, while knockdown of Ets1 promoted apoptosis. Further, the luciferase reporter assay showed that miR-208b-3p could inhibit Ets1 expression.<h4>Conclusion</h4>LUT pretreatment conveys anti-apoptotic effects after myocardial I/R injury by decreasing miR-208b-3p and increasing Ets1 expression levels.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144877&type=printable |
| spellingShingle | Chen Bian Tongda Xu Hong Zhu Defeng Pan Yang Liu Yuanyuan Luo Pei Wu Dongye Li Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p. PLoS ONE |
| title | Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p. |
| title_full | Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p. |
| title_fullStr | Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p. |
| title_full_unstemmed | Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p. |
| title_short | Luteolin Inhibits Ischemia/Reperfusion-Induced Myocardial Injury in Rats via Downregulation of microRNA-208b-3p. |
| title_sort | luteolin inhibits ischemia reperfusion induced myocardial injury in rats via downregulation of microrna 208b 3p |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144877&type=printable |
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