A CREB-mediated increase in miRNA let-7f during prolonged β-agonist exposure: a novel mechanism of β2-adrenergic receptor down-regulation in airway smooth muscle.

ABSTRACT: β2-Adrenergic receptors (β2ARs) desensitize during continuous agonist activation, which manifests clinically as tachyphylaxis. β-Agonist desensitization of β2ARs in human airway smooth muscle (HASM) cells is recognized in the treatment of asthma and may be related to poor outcomes. Rapid events in desensitization include receptor phosphorylation and internalization, but mechanisms responsible for the decrease in receptor protein after prolonged agonist exposure (down-regulation) are ill defined. The microRNA (miRNA) let-7f regulates β2AR expression by translational repression. In cultured HASM cells from nonasthmatic and asthmatic lungs, 18 h of β-agonist exposure increased let-7f by 2-3-fold, concomitant with a ∼90% decrease in β2ARs. Inhibition of let-7f attenuated this down-regulation r

SUBMITTER: Kim D 

PROVIDER: S-EPMC5998966 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature