HORMONAL REGULATION OF ANGIOTENSINOGEN GENE

我的实验室的长期目标是表征基本的 血压调节和血液流动的机制。现在是时候了 越来越明显的是，组织特异性系统发挥着 对血压的调节有巨大的影响，可能 在高血压的发生中起着重要作用。我们已经专注于 血管紧张素原在循环肾素中的重要作用 血管紧张素系统，也可在肝外组织合成。 很可能当地一代的安根人会有深刻的 在没有变化的情况下的生理和病理效应 循环血管。对血管紧张素表达的控制和对 当地发电系统的功能有望得到阐明 通过所描述的实验。我们的目标是确定 当地的安根人一代。中枢神经系统的功能意义 将通过详细的解剖定位来阐明生成(在 原位杂交和穿孔活检研究)与 血管紧张素的生理和药理调节作用研究 M RNA水平(定量原位杂交和缝隙杂交)。 血管紧张素在肾功能中的可能作用将由以下因素确定 详细的解剖定位(原位杂交)和研究 相关生理操作对血管紧张素基因表达调控的影响。 血管紧张素转运蛋白可能对 血管功能。细胞起源的确定 (内皮与平滑肌)将通过原位完成 杂交。监管将以量化的方式研究 为大脑开发的原位方法。我们的目标是确定 利用细胞培养系统调控血管紧张素基因。我们会 描述荷尔蒙调节(缝隙印迹和核运行 由激素和生长因子在MA10间质细胞和 将结果与在鲁伯H35细胞中获得的结果进行比较。 白纹伊蚊侧翼序列的分离与鉴定 血管紧张素基因是高水平理解组织所必需的 特异性调控，因此我们将克隆编码大鼠的基因 安根。然后我们将确定特定的基因组序列 并对必要的细胞特异性核因子进行表征 进行血管紧张素基因调控。我们将使用CAT分析和凝胶 用于获取关于细胞特定结合的信息的保留方法 因子和调控序列。最后，我们的目标是确定 生长因子在安根生产中的作用。实体瘤作为 以及发育中的组织需要充足的血液流动和 血管化以实现持续生长。自血管生成(生长)以来 现在已经确定了因素，我们的目标是确定 这些因素在血管紧张素基因的调节中起作用。当愤怒时 基因表达的特点如上所述，它将成为可能 对当地一代人的发展做出推断 影响正常的功能或引起病理性的影响。

The long term goal of my laboratory is to characterize the basic mechanisms of blood pressure regulation and blood flow. It is now becoming apparent that tissue specific systems exert a tremendous influence on the regulation of blood pressure and may play a major role in the genesis of hypertension. We have focused on angiotensinogen (angen), important in the circulating renin angiotensin system, but also synthesized in extra-hepatic tissues. It is likely that local generation of angen can have profound physiologic and pathologic effects in the absence of changes in circulating angen. The control of angen expression and the function of local generating systems will hopefully be elucidated by the experiments described. We aim to determine the function of local angen generation. The functional significance of CNS generation will be elucidated by detailed anatomic localization (in situ hybridization and punch biopsy studies) in combination with studies on the physiologic and pharmacologic regulation of angen mRNA levels (quantitative in situ and slot blot hybridization). The possible roles of angen in renal function will be determined by detailed anatomic localization (in situ hybridization) and studies of angen mRNA regulation by relevant physiologic manipulations. Angen may have important autocrine or paracrine influence on blood vessel function. Determination of the cellular origin (endothelium vs. smooth muscle) will be accomplished by in situ hybridization. Regulation will be studied by the quantitative in situ methods developed for brain. We aim to determine the regulation of angen gene using cell culture systems. We will characterize the hormonal regulation (slot blot and nuclear run off) by hormones and growth factors in MA10 Leydig cells and compare the results to those obtained in Reuber H35 cells. Isolation and characterization of the flanking sequences of the angen gene is required for a high level of understanding of tissue specific regulation, thus we will clone the gene encoding rat angen. We then will determine the specific genomic sequences and characterize the cellular specific nuclear factors necessary for angen gene regulation. We will use CAT assays and the gel retention method to gain information about cell specific binding factors and regulatory sequences. Finally we aim to determine the role of growth factors in angen production. Solid tumors as well as developing tissues need adequate blood flow and vascularization for continued growth. Since angiogenesis (growth) factors have now been identified, we aim to determine the role of these factors in the regulation of the angen gene. When angen gene expression is characterized as above, it will become possible to make inferences about the extent to which local generation effects normal function or causes pathologic effects.