Airway smooth muscle cell (ASMC) was known to involve in the pathophysiology of asthma. Schisandrin B was reported to have anti-asthmatic effects in a murine asthma model. However, the molecular mechanism involving in the effect of Schisandrin B on ASMCs remains poorly understood. Sprague-Dawley rats were divided into three groups: rats as the control (Group 1), sensitized rats (Group 2), sensitized rats and intragastric-administrated Schisandrin B (Group 3). The expression of miR-135a and TRPC1 was detected in the rats from three groups. Platelet-derived growth factor (PDGF)-BB was used to induce the proliferation of isolated ASMCs, and the expression of miR-135a and TRPC1 was detected in PDGF-BB-treated ASMCs. Cell viability was examined in ASMCs transfected with miR-135a inhibitor or si-TRPC1. The expression of TRPC1 was examined in A10 cells pretreated with miR-135a inhibitor or miR-135a mimic. In this study, we found that Schisandrin B attenuated the inspiratory and expiratory resistances in sensitized rats. Schisandrin B upregulated the mRNA level of miR-135a and decreased the expression of TRPC1 in sensitized rats. In addition, Schisandrin B reversed the expression of miR-135a and TRPC1 in PDGF-BB-induced ASMCs. Si-TRPC1 abrogated the increasing proliferation of ASMCs induced by miR-135a inhibitor. We also found that miR-135a regulated the expression of TRPC1 in the A10 cells. These results demonstrate that Schisandrin B inhibits the proliferation of ASMCs via miR-135a suppressing the expression of TRPC1.

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Schisandrin B increased miR-150 expression and decreased BCYRN1, and BCYRN1 expression was inhibited by miR-150, which indicated that Schisandrin B could regulate BCYRN1 through miR-150.

Foxa2 is a member of the Forkhead family of nuclear transcription factors that is highly expressed in respiratory epithelial cells of the developing and mature lung. Foxa2 is required for normal airway epithelial differentiation, and its deletion causes goblet-cell metaplasia and Th2-mediated pulmonary inflammation during postnatal development. Foxa2 expression is inhibited during aeroallergen sensitization and after stimulation with Th2 cytokines, when its loss is associated with goblet-cell metaplasia. Mechanisms by which Foxa2 controls airway epithelial differentiation and Th2 immunity are incompletely known. During the first 2 weeks after birth, the loss of Foxa2 increases the production of leukotrienes (LTs) and Th2 cytokines in the lungs of Foxa2 gene-targeted mice. Foxa2 expression inhibited 15-lipoxygenase (Alox15) and increased Alox5 transcription, each encoding key lipoxygenases associated with asthma. The inhibition of the cysteinyl LT (CysLT) signaling pathway by montelukast inhibited IL-4, IL-5, eotaxin-2, and regulated upon activation normal T cell expressed and presumably secreted expression in the developing lungs of Foxa2 gene-targeted mice. Montelukast inhibited the expression of genes regulating mucus metaplasia, including Spdef, Muc5ac, Foxa3, and Arg2. Foxa2 plays a cell-autonomous role in the respiratory epithelium, and is required for the suppression of Th2 immunity and mucus metaplasia in the developing lung in a process determined in part by its regulation of the CysLT pathway.

This study aimed to validate whether transient receptor potential channel1 (TRPC1) and TRPC3 participate in the regulation the proliferation of airway smooth muscle cells (ASMCs) through modulating calcium ion (Ca ) influx in vitro. Chronic model of murine asthma was induced and ASMCs isolated from asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in asthmatic mouse ASMCs and selected for further investigation. Ca concentration and the cell viability of asthmatic mouse ASMCs were significantly higher than that from non- asthma mice, however, TRPC channels blocker SKF96365 alleviated these effects. Furthermore, TRPC1 or TRPC3 overexpression markedly increased Ca concentration and significantly induced the viability of ASMCs; whereas TRPC1 or TRPC3 knockdown exerted the completely conversed effects. Moreover, knockdown of TRPC1 and TRPC3 also exerted different effects on the protein expression of growth-related proteins p-p38, p-JNK, cleaved caspase-3 and Bcl-2, as well as on cell cycle. Finally, we found Ca chelator EGTA or BAPTA-AM significantly diminished the effects of si-TRPC1 and si-TRPC3 on the cell viability, cell cycle, and the protein expression of p-p38, p-JNK, cleaved caspase-3, and Bcl-2 in asthmatic mouse ASMCs. Our findings demonstrated that the effects of TRPC1 and TRPC3 on the cell viability and cell cycle of ASMCs were, at least partially, through regulating Ca influx.