MicroRNA-mediated Downregulation of K+ Channels in Pulmonary Arterial Hypertension.

MicroRNA-mediated Downregulation of K+ Channels in Pulmonary Arterial Hypertension. Am J Physiol Lung Cell Mol Physiol. 2019 Sep 25;: Authors: Babicheva A, Ayon RJ, Zhao T, Ek Vitorin JF, Pohl NM, Yamamura A, Yamamura H, Quinton BA, Ba M, Wu L, Ravellette KS, Rahimi S, Balistrieri F, Harrington A, Vanderpool RR, Thistlethwaite PA, Makino A, Yuan JX Abstract Downregulated expression of K+ channels and decreased K+ currents in pulmonary artery smooth muscle cells (PASMC) have been implicated in the development of sustained pulmonary vasoconstriction and vascular remodeling in patients with idiopathic pulmonary arterial hypertension (IPAH). However, it is unclear exactly how K+ channels are downregulated in IPAH-PASMC. MicroRNAs (miRNAs) are small noncoding RNAs that are capable of posttranscriptionally regulating gene expression by binding to the 3'-untranslated regions (3'-UTR) of their targeted mRNAs. Here we report that specific miRNAs are responsible for the decreased K+ channel expression and function in IPAH-PASMC. We identified 3 miRNAs (miR-29b, miR-138 and miR-222) that were highly expressed in IPAH-PASMC in comparison to normal PASMC (>2.5-fold difference). Selectively upregulated miRNAs are correlated with the decreased expression and attenuated activity of K+ channels. Overexpression of miR-29b, miR-138 or miR-222 in normal PASMC significantly decreased whole-cell K+ currents and downregulated voltage-gated K+ channel 1....
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research