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MicroRNA-133a inhibits norepinephrine-induced cardiac hypertrophy via suppression of PKC signaling

Other Titles
 miR-133a에 의한 노에피네프린으로 유도된 심근비대 억제효과 
 Dept. of Internal Medicine (내과학교실) 
Issue Date
Dept. of Medicine/박사
Cardiac hypertrophy is associated with the development of heart failure and has been known as a predictor for cardiovascular morbidity and mortality. A recent study unveiled potential regulatory roles for microRNA-133a (miR-133a) in cardiac hypertrophy. However, it has not been studied to elucidate the connection between miR-133a and norepinephrine-induced cardiomyocyte hypertrophy. Here, we investigated the expression and functional role of miR-133a in a norepinephrine-induced hypertrophic cardiomyocyte and determined the target of miR-133a in hypertrophic signaling. Neonatal rat cardiomyocytes were isolated, and cardiac hypertrophy was induced by treatment with 10 μM norepinephrine. In this study, we determined that miR-133a plays a pivotal role in the regulation of norepinephrine-induced cardiac hypertrophy. miR-133a expression is inversely related to cardiac hypertrophy, and the treatment with miR-133a mimics before norepinephrine management prevents norepinephrine-induced cardiac hypertrophy. Second, we found that the direct target of miR-133a is Protein Kinase C δ (PKCδ), which was confirmed by both Luciferase assay and Western blot analysis. We found no relationship between miR-133a and G protein. Finally, after transfection with miR-133a, MEK and ERK, which are in the downstream pathway, and proto-oncogenes such as c-fos, c-myc and c-jun were down-regulated in hypertrophic cardiomyocytes, suggesting that PKCδ is a novel target of miR-133a in cardiomyocytes, and that administration of or treatment with miR-133a mimics could be used in the future as a therapeutic application in the clinical setting
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 3. Dissertation
Yonsei Authors
Moon, Jae Youn(문재연)
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