Role of miRNAs in the development of bronchial smooth muscle hyperresponsiveness in allergic asthma

本研究旨在阐明哮喘患者气道高反应性的发生机制。在过敏性哮喘小鼠的支气管平滑肌中，观察到RhoA蛋白的上调和miR-140- 3 p的下调。在培养的人支气管平滑肌细胞中，当内源性miR-140- 3 p的功能被其受体抑制时，观察到RhoA蛋白的上调。用白细胞介素-13处理细胞引起RhoA蛋白的上调和miR-140- 3 p的下调。这些结果表明，RhoA蛋白表达在支气管平滑肌细胞中受到miR-140- 3 p的负调控。IL-13在哮喘患者气道中的表达增加可能至少部分地有助于miR-140- 3 p的减少，导致RhoA蛋白上调和气道平滑肌收缩增强。

Current study was carried out to make clear the mechanism(s) of development of airway hyperresponsiveness in asthmatics. In bronchial smooth muscles of mice with allergic asthma, an up-regulation of RhoA protein and a down-regulation of miR-140-3p were observed. In cultured human bronchial smooth muscle cells, an up-regulation of RhoA protein was observed when the function of endogenous miR-140-3p was inhibited by its antagomir. Treatment of the cells with interleukin-13 caused an up-regulation of RhoA protein and a down-regulation of miR-140-3p. These findings suggest that RhoA protein expression is negatively regulated by miR-140-3p in bronchial smooth muscle cells. The increased expression of interleukin-13 in the airways of asthmatics might, at least in part, contribute to the reduction of miR-140-3p, resulting in an up-regulation of RhoA protein and augmented smooth muscle contraction of the airways.