Molecules
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Mechanical stimulation regulates endothelial cell (EC) functions through the modulation of signaling networks and gene expression. Our recent studies have identified that shear stress regulation of microRNAs (miRs)-19a, 23b and 27b, led to the modulation of EC proliferation. However, the underlying molecular mechanisms by which shear stress regulates these miRs have not been explored. ⋯ The knockdown of miR-19a using antagomir-19a oligonucleotide (AM19a) decreased the shear-induced PI3K activation; whereas AM-23b, 27b reduced the shear-induced MAPK activation. Furthermore, the overexpression of miR-19a overrode the suppressive effects of PI3K inhibitors on shear-induced PI3K activation; the overexpression of miR-23b, 27b had similar effects on ERK activations, but had little effect on P38 and JNK activation. Our findings suggest a positive feedback loop whereby PI3K and MAPK mediate the shear regulation of miR expression, which in turn modulates the shear-regulated PI3K/MAPK signaling events in ECs.