Background: Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can down-regulate SOCE. Objective: We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Methods: Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the SARAF gene + GFP or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA(siRNA) or SARAF-specific siRNA respecitvely. The proliferation, migration rate, hypertrophy and SOCE activity of hASMCs were examined with cell counting kit 8, wound healing test, bright field imaging and Ca²⁺ fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time-PCR. Results: Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy and SOCE activity in hASMCs. Conclusions: SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.

中文翻译：

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商店经营的钙进入相关调节因子调节哮喘小鼠模型的气道炎症和气道重塑

背景：储存操作的钙进入（SOCE）参与哮喘气道炎症和重塑的发病机制。存储操作的钙进入相关调节因子 (SARAF) 可以下调 SOCE。目的：我们试图研究 SARAF 在调节哮喘小鼠模型气道炎症和重塑中的作用，以及在人气道平滑肌细胞 (hASMCs) 的功能调节中的作用。方法：以卵清蛋白致敏Balb/c小鼠，建立哮喘小鼠模型。用慢病毒转染小鼠，慢病毒表达 SARAF 基因 + GFP 或阴性对照基因 + GFP。用动物肺功能系统测量气道阻力。通过组织学染色评估气道炎症和重塑。体外培养的 hASMCs 分别用乱序小干扰 RNA(siRNA) 或 SARAF 特异性 siRNA 转染。用细胞计数试剂盒 8、伤口愈合试验、明场成像和 Ca 检测 hASMC 的增殖、迁移率、肥大和 SOCE 活性²⁺荧光成像，分别。通过定量实时PCR测量SARAF表达。结果：哮喘小鼠模型显示肺中 SARAF mRNA 表达降低。SARAF 过表达减弱了气道炎症、阻力和重塑。用siRNA下调SARAF表达促进hASMCs的增殖、迁移、肥大和SOCE活性。结论：SARAF通过钝化SOCE对哮喘小鼠模型的气道炎症和重塑发挥保护作用；SARAF 也可能是 hASMCs 的功能调节因子。