Hormonal regulation of rat adrenomedullin gene in vasculature.
Hormonal regulation of rat adrenomedullin gene in vasculature.
复制标题
血管系统中大鼠肾上腺髓质素基因的激素调节。
作者：
T. Imai;Y. Hirata;M. Iwashina;F. Marumo
肾上腺髓质素(Adrenomedullin，AM)是从人嗜铬细胞瘤中分离出来的一种新的血管扩张肽，后来被证明在肾上腺、肺、心脏、肾脏和主动脉等多种组织中都有表达。为确定血管AM基因的表达是否受激素控制，以聚合酶链式反应克隆的大鼠AM互补DNA为探针，采用Northern印迹法检测了地塞米松(DEX)和T3对培养的大鼠血管内皮细胞和血管平滑肌细胞(VSMCs)AM信使RNA(MRNA)表达的影响。地塞米松的剂量和时间依赖地增加内皮细胞和VSMC的稳态AM mRNA水平。T3适度诱导两种细胞AM mRNA的表达，而T3的生物活性异构体RT3不影响AM mRNA的表达。糖皮质激素受体拮抗剂(RU 38486)可阻断地塞米松诱导的两种细胞的AM基因表达，而雌二醇和睾酮均不影响AM基因的表达。放线菌素D抑制基础和刺激的AM基因表达，而放线菌亚胺显著增加稳态基因表达水平(超诱导)。DEX刺激VSMC基础和刺激AM基因表达的半衰期约为1h，而放线菌胺诱导的AM基因表达在6h后几乎没有衰退。我们的研究表明，血管内皮细胞和血管平滑肌细胞表达的AM基因类似地受糖皮质激素和甲状腺激素的调节，而AM基因的超诱导很可能是由于增加了mRNA的稳定性。
Adrenomedullin (AM), a novel vasodilatory peptide originally isolated from human pheochromocytoma, has subsequently been shown to be expressed in a variety of tissues, such as adrenal gland, lung, heart, kidney, and aorta. To determine whether vascular AM gene expression is under hormonal control, the effects of dexamethasone (DEX) and T3 on AM messenger RNA (mRNA) expression were tested in cultured rat vascular endothelial cells and smooth muscle cells (VSMCs) by Northern blot analysis using polymerase chain reaction-cloned rat AM complementary DNA as a probe. DEX dose and time dependently increased steady-state AM mRNA levels in both endothelial cells and VSMC. T3 modestly induced AM mRNA expression in both cells, whereas rT3, a biologically inactive isomer of T3, failed to affect AM mRNA expression. A glucocorticoid receptor antagonist (RU 38486) blocked DEX-induced AM mRNA expression in both cells, whereas neither estradiol nor testosterone affected AM mRNA expression. Actinomycin D abolished basal as well as stimulated AM mRNA expression by T3, whereas cycloheximide markedly increased steady state mRNA levels (superinduction). The approximate half-lives of basal and stimulated expression of AM mRNA by DEX in VSMC were within 1 h. In contrast, there was little, if any, decay in cycloheximide-induced AM mRNA expression over 6 h. Our study demonstrates that the AM gene expressed by vascular endothelial and smooth muscle cells is similarly regulated by glucocorticoid and possibly by thyroid hormone, and that superinduction of AM mRNA is most likely due to increased mRNA stability.
DOI：
10.1073/pnas.83.6.1670
发表时间：
1986-03-01
影响因子：
11.1
作者：
CAPUT, D;BEUTLER, B;CERAMI, A
通讯作者：
CERAMI, A