SOX18 enhances the proliferation and migration of airway smooth muscle cells induced by tumor necrosis factor-α via the regulation of Notch1 signaling

Abstract

Childhood asthma is a frequent chronic disease of pediatric populations. The excessive proliferation and migration of airway smooth muscle cells contribute to airway remodeling during asthma pathogenesis. Sex-determining region on the Y chromosome-related high mobility group box 18 (SOX18) has been reported to be over-expressed in asthma. However, whether SOX18 plays a role in modulating the airway remodeling of asthma is not fully understood. The purposes of this work were to assess the potential role of SOX18 in modulating airway remodeling using tumor necrosis factor-α (TNF-α)-stimulated airway smooth muscle cells in vitro. Our results showed that SOX18 expression was increased following TNF-α stimulation in airway smooth muscle cells. The silencing of SOX18 markedly prohibited the proliferation and migration of airway smooth muscle cells induced by TNF-α, whilst the over-expression of SOX18 produced the opposite effects. Further investigation revealed that SOX18 promoted the expression of Notch1, and enhanced the activation of Notch1 signaling in airway smooth muscle cells stimulated by TNF-α. The inhibition of Notch1 markedly diminished SOX18-over-expression-evoked promotion effects on TNF-α-induced proliferation and migration of airway smooth muscle cells. In addition, the reactivation of Notch1 signaling markedly reversed the SOX18-silencing-induced suppressive effect on the TNF-α-induced proliferation and the migration of airway smooth muscle cells. In summary, the findings of this work demonstrate that SOX18 regulates the proliferation and migration of airway smooth muscle cells induced by TNF-α via the modulation of Notch1 signaling. This study indicates a potential role for SOX18 in promoting airway remodeling during asthma pathogenesis.