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(S)。在过敏性哮喘小鼠的支气管平滑肌中，RhoA蛋白表达上调，miR-140-3p表达下调。在培养的人支气管平滑肌细胞中，当内源性miR-140-3p的功能被其拮抗剂抑制时，RhoA蛋白表达上调。经IL-13处理后，RhoA蛋白表达上调，miR-140-3p表达下调。这些发现表明，MIR-140-3p对RhoA蛋白的表达具有负性调节作用。哮喘患者呼吸道IL-13的表达增加，可能至少部分参与了miR-140-3p的表达减少，导致RhoA蛋白表达上调，增强了呼吸道的平滑肌收缩。

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.