YAP1, targeted by miR-375, enhanced the pro-angiogenesis of airway smooth muscle cells in asthma via STAT3 activation.

YAP1 was previously reported to regulate the development of multiple tumors, angiogenesis included. Angiogenesis was a specific process of remodeling in asthma. In a recent study, YAP1 was correlated with the progression of asthma. However, the role of YAP1 in airway smooth muscle cell and the asthmatic airway angiogenesis was unclear. In the present study, we used cytokine-stimulated airway smooth muscle cells as asthma cell model in vitro. The results showed a significant up-regulation of YAP1 in asthmatic airway smooth muscle tissue and cytokine-stimulated asthmatic cell model by Western blot. The experimental results of YAP1 loss-of-function combined with STAT3 inhibitor (WP1066) showed that YAP1 knockdown inhibited the expression of VEGF by deactivating STAT3 in cytokine-stimulated ASM cells, which hindered the pro-angiogenesis ability of ASM cells. Besides, by combining prediction and binding site mutation along with luciferase reporter gene experiments, we confirmed direct binding between miR-375 and YAP1. Based on that, the decreased expression level of miR-375 was found to be correlated with the pathogenesis of asthma. Finally, miR-375 was verified to participate in the YAP1-regulated pro-angiogenesis ability of ASM cells. To sum up, we provided the evidence that YAP1 directly binds to miR-375 and takes part in the regulation of the pro-angiogenic ability of ASM cells by activating STAT3 and VEGF signaling.