RESUMO
AIMS: Augmented smooth muscle contractility of the airways associated with an increased expression of RhoA, a monomeric GTPase responsible for Ca2+ sensitization of contraction, is one of the causes of airway hyperresponsiveness. However, the mechanism of the altered properties of airway smooth muscle cells, including the RhoA upregulation, is not fully understood. This study aims to define functional role of a long non-coding RNA MALAT1 in the RhoA expression and development of bronchial smooth muscle (BSM) hyper-contractility. MAIN METHODS: Cultured human BSM cells were transfected with MALAT1 antisense oligonucleotide (AS), miR-133a-3p mimic, and/or inhibitor, and then stimulated with interleukin-13 (IL-13). In animal experiments, the ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. KEY FINDINGS: Treatment of the cells with IL-13 induced an increase in RhoA protein. Either MALAT1 AS or miR-133a-3p mimic transfection inhibited the IL-13-induced upregulation of RhoA. The inhibitory effect of MALAT1 AS was abolished by co-transfection with miR-133a-3p inhibitor. In BSMs of the murine asthma model, upregulations of Malat1 and RhoA protein were observed concomitantly with downregulation of miR-133a-3p. SIGNIFICANCE: These findings suggest that MALAT1 positively regulates RhoA protein expression by inhibiting miR-133a-3p in BSM cells, and that its upregulation causes the RhoA upregulation, resulting in an augmented BSM contractility.
