Mechanisms for inducible control of angiotensinogen gene transcription
Mechanisms for inducible control of angiotensinogen gene transcription
复制标题
DOI：
10.1161/01.hyp.27.3.465
复制
发表时间：
1996-03-01
期刊：
影响因子：
8.3
通讯作者：
Li, JY
中科院分区：
文献类型：
--
作者：
Brasier, AR;Li, JY
血管内肾素-血管紧张素系统是一种内分泌系统，旨在维持心血管稳态，以应对低血压。在正常情况下，血浆中循环的血管紧张素原浓度是血管紧张素I形成的最大速度的速率限制。在肝脏中，循环血管紧张素原合成的主要部位，血管紧张素原的表达受到精确的激素控制。我们综述了激素影响血管紧张素原表达的转录调控机制。肾上腺源性糖皮质激素使糖皮质激素受体移位到细胞核中。它又与两个糖皮质激素反应元件结合并刺激血管紧张素原基因转录。由于巨噬细胞衍生的细胞因子白细胞介素-1和肿瘤坏死因子-α，炎症激活血管紧张素原转录。这些细胞因子改变了两个转录因子家族的丰度，这两个家族结合血管紧张素原启动子（急性期反应元件）中的单个调节位点。这些蛋白质包括核因子-κ B复合物和CCAAT/增强子结合蛋白家族。通过产生血管紧张素II激活肾素-血管紧张素系统，导致血管紧张素原合成的反馈刺激（"正反馈环"）。我们发现核因子-κ B转录因子受血管紧张素II调节，这一发现为正反馈环中血管紧张素原基因合成的转录组分提供了一种机制。这些研究强调的概念，诱导血管紧张素原基因由不同的生理刺激介导的序列特异性转录因子的核丰度的变化。细胞因子和血管紧张素II诱导的信号通路在核因子-κ B转录因子上的细胞内会聚为血管紧张素和血管紧张素激活的第二信使通路之间的"串扰"提供了一个点。
The intravascular renin-angiotensin system is an endocrine system designed to maintain cardiovascular homeostasis in response to hypotension. Under normal conditions, angiotensinogen concentrations circulating in the plasma are rate limiting for the maximum velocity of angiotensin I formation. In the liver, the major site of circulating angiotensinogen synthesis, angiotensinogen expression is under exquisite hormonal control. We review the mechanisms by which hormones effect transcriptional control of angiotensinogen expression. Adrenal-derived glucocorticoids produce the translocation of the glucocorticoid receptor into the nucleus. It in turn binds to two glucocorticoid response elements and stimulates angiotensinogen gene transcription. Inflammation activates angiotensinogen transcription as a result of the macrophage-derived cytokines interleukin-1 and tumor necrosis factor-alpha. These cytokines change the abundance of two transcription factor families that bind a single regulatory site in the angiotensinogen promoter, the acute-phase response element. These proteins include the nuclear factor-kappa B complex and the CCAAT/enhancer binding protein family. Activation of the renin-angiotensin system, through production of angiotensin II, results in feedback stimulation of angiotensinogen synthesis (the ''positive feedback loop''). We have discovered that the nuclear factor-kappa B transcription factor is regulated by angiotensin II, a finding that provides a mechanism for the transcriptional component of angiotensinogen gene synthesis in the positive feedback loop. These studies underscore the concept that induction of the angiotensinogen gene by diverse physiological stimuli is mediated through changes in the nuclear abundance of sequence-specific transcription factors. The intracellular convergence of cytokine- and angiotensin II-induced signaling pathways on the nuclear factor-kappa B transcription factor provides a point for ''cross talk'' between angiotensin- and cytokine-activated second messenger pathways.