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Cell Death Dis. 2014 Apr 10;5:e1171. doi: 10.1038/cddis.2014.141.

Cardiac hypertrophy is negatively regulated by miR-541.

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Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Department of Pharmacology, University of California, Irvine, CA 92697, USA.
Signal Transduction Laboratory, Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.


Heart failure is a leading cause of death in aging population. Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading, but continuous cardiac hypertrophy is able to induce heart failure. We found that the level of miR-541 was decreased in angiotensin II (Ang-II) treated cardiomyocytes. Enforced expression of miR-541 resulted in a reduced hypertrophic phenotype upon Ang-II treatment in cellular models. In addition, we generated miR-541 transgenic mice that exhibited a reduced hypertrophic response upon Ang-II treatment. Furthermore, we found miR-541 is the target of microphthalmia-associated transcription factor (MITF) in the hypertrophic pathway and MITF can negatively regulate the expression of miR-541 at the transcriptional levels. MITF(ce/ce) mice exhibited a reduced hypertrophic phenotype upon Ang-II treatment. Knockdown of MITF also results in a reduction of hypertrophic responses after Ang-II treatment. Knockdown of miR-541 can block the antihypertrophic effect of MITF knockdown in cardiomyocytes upon Ang-II treatment. This indicates that the effect of MITF on cardiac hypertrophy relies on the regulation of miR-541. Our present study reveals a novel cardiac hypertrophy regulating pathway that was composed of miR-541 and MITF. Modulation of their levels may provide a new approach for tackling cardiac hypertrophy.

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