Pathological growth of cardiomyocytes (hypertrophy) is a major determinant for the development of heart failure, one of the leading medical causes of mortality worldwide. Here we show that the ...microRNA (miRNA)-212/132 family regulates cardiac hypertrophy and autophagy in cardiomyocytes. Hypertrophic stimuli upregulate cardiomyocyte expression of miR-212 and miR-132, which are both necessary and sufficient to drive the hypertrophic growth of cardiomyocytes. MiR-212/132 null mice are protected from pressure-overload-induced heart failure, whereas cardiomyocyte-specific overexpression of the miR-212/132 family leads to pathological cardiac hypertrophy, heart failure and death in mice. Both miR-212 and miR-132 directly target the anti-hypertrophic and pro-autophagic FoxO3 transcription factor and overexpression of these miRNAs leads to hyperactivation of pro-hypertrophic calcineurin/NFAT signalling and an impaired autophagic response upon starvation. Pharmacological inhibition of miR-132 by antagomir injection rescues cardiac hypertrophy and heart failure in mice, offering a possible therapeutic approach for cardiac failure.
Prox 1, a likely mouse homologue of the Drosophila homeobox gene prospero has been cloned and its expression pattern analyzed during development. In Drosophila, prospero is expressed in the ...developing CNS, lens-secreting cone cells of the eye, and midgut. In the mouse, Prox 1 is expressed in many of the same tissues: young neurons of the subventricular region of the CNS, developing eye lens and pancreas. Expression is also detected in the developing liver and heart, as well as transiently in the skeletal muscles. The similarities in protein sequence and expression patterns between the mouse and fly cognate genes suggest that Prox 1 may play, among others, a fundamental role in early development of the murine CNS.
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