Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.
Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.
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DOI：
10.1155/2012/307838
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Ammit AJ
中科院分区：
文献类型：
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作者：
Allen JC;Seidel P;Schlosser T;Ramsay EE;Ge Q;Ammit AJ
气道平滑肌增生是哮喘患者气道重构的一个特征。我们检测了皮质类固醇地塞米松对非哮喘患者和受有丝分裂原血小板衍生生长因子BB刺激的哮喘患者ASM细胞中G1细胞周期进程的关键调节因子-周期蛋白d1表达的抗增殖效果。非哮喘组细胞cyclin D1 mRNA和蛋白表达受到抑制，而哮喘组细胞cyclin D1表达对地塞米松的抑制具有抗性。这与糖皮质激素受体易位的抑制作用无关。我们的研究结果证实了糖皮质激素仅在非哮喘受试者的ASM细胞中抑制丝裂原诱导的增殖，并表明哮喘患者中存在糖皮质激素不敏感的增殖途径。
Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G1 cell cycle progression—cyclin D1—in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.