PROSTATIC SMOOTH MUSCLE GENE EXPRESSION

前列腺平滑肌基因表达

基本信息

批准号：
6239126
负责人：
VICTOR K LIN
金额：
$ 18.12万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-11 至 1999-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6239126
关键词：
RNase protection assay SDS polyacrylamide gel electrophoresis androgens antiadrenergic agents antibody benign prostate hyperplasia enzyme inhibitors extracellular matrix gene expression hormone regulation /control mechanism immunocytochemistry laboratory rabbit molecular cloning myosins northern blottings nucleic acid sequence oxidoreductase prostate smooth muscle sympathetic nervous system western blottings

RNase protection assay SDS polyacrylamide gel electrophoresis androgens antiadrenergic agents antibody benign prostate hyperplasia enzyme inhibitors extracellular matrix gene expression hormone regulation /control mechanism immunocytochemistry laboratory rabbit molecular cloning myosins northern blottings nucleic acid sequence oxidoreductase prostate smooth muscle sympathetic nervous system western blottings

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项目摘要

Smooth muscle (SM) is a major component of the hyperplastic stroma in benign prostatic hyperplasia (BPH). In many muscle systems, muscle cell contractile protein and extracellular matrix (ECM) gene expression are modulated by alpha-adrenergic and androgenic signals. Given the known importance of androgens and sympathetic innervation in the pathophysiology of BPH, the potential role of these regulatory signals in the prostate is obvious. Unfortunately, the prostatic smooth muscle cell has been largely neglected in recent studies of prostate cell and molecular biology. We propose to characterize the expression of an important contractile protein in the prostatic smooth muscle cell, myosin heavy chain (MHC), and determine whether androgenic and alpha adrenergic signals regulate expression. In addition, prostatic ECM will be characterized at the protein biochemical level and similar regulatory issues studied. Protein biochemical, immunohistochemical, and molecular biologic techniques will be utilized to address the following specific aims; 1) Cloning of human smooth muscle MHC, 2) Development of monospecific antibodies for immunoblot and immunohistochemical analysis, 3) Characterization of MHC expression in the prostate, 4) Characterization of non-muscle MHC expression in the prostate, 5) Regulation of MHC and ECM expression in the human prostate by alpha- adrenergic and androgenic signals, and 6) Characterization and regulation of ECM expression. These studies should provide significant new insight into the role of the prostatic smooth muscle cell in the pathophysiology of BPH.

平滑肌（SM）是增生基质的主要组成部分良性前列腺增生（BPH）。在许多肌肉系统中，肌肉细胞收缩蛋白和细胞外基质（ECM）基因表达是由α-肾上腺素和雄激素信号调节。鉴于已知雄激素和同情神经的重要性 BPH的病理生理学，这些调节信号的潜在作用在前列腺中很明显。不幸的是，前列腺平滑肌在前列腺细胞和分子生物学。我们建议表征前列腺平滑肌细胞中的重要收缩蛋白肌球蛋白重链（MHC），并确定雄激素和α肾上腺素是否能信号调节表达。此外，前列腺ECM将是在蛋白质生化水平和类似调节的表征研究的问题。蛋白质生化，免疫组织化学和分子生物技术将用于解决以下特定目标； 1）人类平滑肌MHC的克隆，2）开发免疫印迹和免疫组织化学分析的单特异性抗体， 3）前列腺中MHC表达的表征，4）前列腺中非肌肉MHC表达的表征，5）通过α-调节人类前列腺中MHC和ECM的表达肾上腺素和雄激素信号，以及6）表征和调节 ECM表达。这些研究应提供重要的新见解进入前列腺平滑肌细胞在病理生理学中的作用 BPH。