Glucocorticoids decrease the synthesis of type I procollagen mRNAs.

Glucocorticoids decrease the synthesis of type I procollagen mRNAs.
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糖皮质激素减少 I 型前胶原 mRNA 的合成。

DOI:
10.1021/bi00359a018
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发表时间:
1986
期刊:
影响因子:
2.9
通讯作者:
Cutroneo,KR
Cutroneo,KR
中科院分区:
生物学3区
文献类型:
--
作者:
Cockayne,D;SterlingJr,KM;Shull,S;Mintz,KP;Illeyne,S;Cutroneo,KR

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Department of Biochemistry,College of Medicine,University of Vermont,Burlington,Vermont 05405 Received October 16,1985; Revised Mandarin pt Received February 18,1986摘要:糖皮质激素选择性降低动物和人类皮肤成纤维细胞中的前胶原合成。/ 3-肌动蛋白含量和β-肌动蛋白mRNA不受糖皮质激素处理的鸡皮肤成纤维细胞。在鸡皮肤成纤维细胞中糖皮质激素对前胶原合成的抑制作用与总细胞I型前胶原mRNA的减少有关。地塞米松的这些作用是受体介导的,如通过用糖皮质激素拮抗剂孕酮和RU-486以及激动剂/3-二氢皮质醇预处理所确定的。地塞米松对鸡皮肤成纤维细胞的生长有轻微但显著的抑制作用。这种皮质类固醇降低I型前胶原mRNA在细胞核、细胞质和多核糖体中稳态水平的能力各不相同。地塞米松处理后24 h,在细胞核和细胞质亚细胞组分中观察到I型前胶原mRNA的最大减少。通过对总核RNA的北方印迹分析测定,I型前胶原hnRNA也减少。总细胞I型前胶原mRNA的合成通过地塞米松治疗可逆地降低。此外,在细胞培养物中加入放射性核苷和地塞米松后,总核I型前胶原mRNA序列的合成在2、4和24小时减少。虽然地塞米松处理的鸡皮肤成纤维细胞中pro a1(1)和pro a2(I)mRNA的合成减少,但细胞总前胶原mRNA的降解没有改变,而细胞总RNA的降解稳定。这些数据表明,地塞米松介导的减少前胶原合成的鸡胚皮肤成纤维细胞的结果从前胶原基因表达的调节。
Department of Biochemistry, College of Medicine, University of Vermont, Burlington, Vermont 05405 Received October 16, 1985; Revised Manuscript Received February 18, 1986 abstract: Glucocorticoids selectively decrease procollagen synthesis in animal and human skin fibroblasts./3-Actin content and/3-actin mRNA are not affected by glucocorticoid treatment of chick skin fibroblasts. The inhibitory effect of glucocorticoids on procollagen synthesisis associated with a decrease in total cellular type I procollagen mRNAs in chick skin fibroblasts. These effects of dexamethasone are receptor mediated as determined by pretreatment with the glucocorticoid antagonists progesterone and RU-486 and with the agonist/3-dihydrocortisol. Dexamethasone has a small but significant inhibitory effect on cell growth of chick skin fibroblasts. The ability of this corticosteroid to decrease the steady-state levels of type I procollagen mRNAs innuclei, cytoplasm, and polysomes varies. The largest decrease of type I procollagen mRNAs is observed in the nuclear and cytoplasmic subcellularfractions 24 h after dexamethasone treatment. Type I procollagen hnRNAs are also decreased as determined by Northern blot analysis of total nuclear RNA. The synthesis of total cellular type I procollagen mRNAs is reversibly decreased by dexamethasone treatment. In addition thesynthesis of total nuclear type I procollagen mRNA sequences is decreased at 2, 4, and 24 h following the addition of radioactive nucleoside and dexamethasone to cell cultures. Although the synthesis of pro a 1 (1) and pro a2 (I) mRNAs is decreased in dexmethasone-treated chick skin fibroblasts, thedeg-radation of the total cellular procollagen mRNAs is not altered while the degradation of total cellularRNA is stabilized. These data indicate that the dexamethasone-mediated decrease of procollagen synthesis in embryonic chick skin fibroblasts results from the regulation of procollagen gene expression.