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首页> 外文期刊>Allergy >Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells
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Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells

机译：1-磷酸鞘氨醇诱导气道平滑肌细胞的重塑反应

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Methods Airway smooth muscle cells grown from bronchial biopsies of healthy and asthmatic individuals were exposed to S1P. Gene expression was analysed using microarray, real-time PCR and Western blotting. Receptor signalling and function were determined by mRNA knockdown and intracellular calcium mobilization experiments.Results S1P potently regulated the expression of more than 80 genes in human ASM cells, including several genes known to be involved in the regulation of cell proliferation and airway remodelling (HBEGF, TGFB3, TXNIP, PLAUR, SERPINE1, RGS4). S1P acting through S1P2 and S1P3 receptors activated intracellular calcium mobilization and extracellular signal-regulated and Rho-associated kinases to regulate gene expression. S1P-induced responses were not inhibited by corticosteroids and did not differ significantly between ASM cells from healthy and asthmatic individuals.Conclusion S1P induces a steroid-resistant, pro-remodelling pathway in ASM cells. Targeting S1P or its receptors could be a novel treatment strategy for inhibiting airway remodelling in asthma.Background Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one of the most characteristic features of airway remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested to affect airway remodelling by stimulation of human ASM cell proliferation.Objective To investigate the effect of S1P on signalling and regulation of gene expression in ASM cells from healthy and asthmatic individuals.
机译：方法将健康人和哮喘人的支气管活检组织中生长的气道平滑肌细胞暴露于S1P中。使用微阵列，实时PCR和Western印迹分析基因表达。结果：S1P可以有效调节人ASM细胞中80多个基因的表达，其中包括一些已知与细胞增殖和气道重塑有关的基因（HBEGF， TGFB3，TXNIP，PLAU，SERPINE1，RGS4）。通过S1P2和S1P3受体发挥作用的S1P激活细胞内钙动员以及细胞外信号调节和Rho相关激酶来调节基因表达。 S1P诱导的反应不受皮质类固醇抑制，健康人和哮喘患者的ASM细胞之间也没有显着差异。结论S1P诱导ASM细胞中类固醇抗性，促重塑途径。靶向S1P或其受体可能是抑制哮喘气道重塑的一种新型治疗策略。背景气道平滑肌（ASM）细胞增殖增加导致增生和ASM质量增加是哮喘气道重塑的最特征之一。有人提出了一种生物活性脂质鞘氨醇-1-磷酸（S1P）通过刺激人ASM细胞增殖来影响气道重塑。目的研究S1P对健康人和哮喘人ASM细胞信号转导和基因表达调控的作用。 。

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