Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells.
Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells.
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DOI：
10.1111/all.12489
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发表时间：
2014-11
期刊：
影响因子：
12.4
通讯作者：
Woszczek G
中科院分区：
文献类型：
--
作者：
Fuerst E;Foster HR;Ward JP;Corrigan CJ;Cousins DJ;Woszczek G
气道平滑肌 (ASM) 细胞增殖增加导致增生和 ASM 质量增加，这是哮喘气道重塑的最典型特征之一。一种生物活性脂质，1-磷酸鞘氨醇 (S1P)，被认为可以通过刺激人类 ASM 细胞增殖来影响气道重塑。研究 S1P 对健康和哮喘个体 ASM 细胞中基因表达信号传导和调节的影响。从健康和哮喘个体的支气管活检中生长的气道平滑肌细胞暴露于 S1P。使用微阵列、实时PCR和蛋白质印迹分析基因表达。通过 mRNA 敲低和细胞内钙动员实验确定受体信号传导和功能。 S1P 有效调节人类 ASM 细胞中 80 多个基因的表达，包括已知参与细胞增殖和气道重塑调节的几种基因（HBEGF、TGFB3、TXNIP、PLAUR、SERPINE1、RGS4）。 S1P 通过 S1P2 和 S1P3 受体发挥作用，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的抑制，并且健康个体和哮喘个体的 ASM 细胞之间没有显着差异。 S1P 在 ASM 细胞中诱导类固醇抗性、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治疗策略。
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. To investigate the effect of S1P on signalling and regulation of gene expression in ASM cells from healthy and asthmatic individuals. 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. 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. 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.
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影响因子：
14.2
作者：
Price, Megan M.;Oskeritzian, Carole A.;Falanga, Yves T.;Harikumar, Kuzhuvelil B.;Allegood, Jeremy C.;Alvarez, Sergio E.;Conrad, Daniel;Ryan, John J.;Milstien, Sheldon;Spiegel, Sarah
通讯作者：
Spiegel, Sarah
影响因子：
20.1
作者：
Schulze, PC;De Keulenaer, GW;Lee, RT
通讯作者：
Lee, RT
DOI：
10.1164/ajrccm.164.supplement_2.2106066
发表时间：
2001-11-15
影响因子：
24.7
作者：
Fahy, JV
通讯作者：
Fahy, JV
影响因子：
14.2
作者：
Kelly, Margaret M.;O'Connor, Terence M.;O'Byrne, Paul M.
通讯作者：
O'Byrne, Paul M.
影响因子：
158.5
作者：
Brightling, CE;Bradding, P;Pavord, ID
通讯作者：
Pavord, ID