PROSTATIC SMOOTH MUSCLE GENE EXPRESSION

前列腺平滑肌基因表达

• 批准号: 6105584
• 负责人: VICTOR K LIN
• 金额: --
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-20 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6105584
• 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

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）是增生性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-肾上腺素能和雄激素信号调节。 鉴于已知 雄激素和交感神经支配的重要性 BPH的病理生理学，这些调节信号的潜在作用 在前列腺是显而易见的。 不幸的是前列腺平滑肌 在最近的前列腺细胞研究中， 分子生物学 我们建议对一个 前列腺平滑肌细胞中重要的收缩蛋白，肌球蛋白 重链（MHC），并确定是否雄激素和α肾上腺素能 信号调节表达。 此外，前列腺ECM将 在蛋白质生化水平和类似的调节 研究的问题。 蛋白质生化、免疫组织化学和分子生物学 生物技术将用于解决以下具体问题 目的：1）克隆人平滑肌MHC，2）开发 用于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） 人前列腺组织中MHC和ECM表达的调控 肾上腺素能和雄激素信号，以及6）表征和调节 ECM的表达。 这些研究应该提供重要的新见解 前列腺平滑肌细胞在病理生理学中的作用 的BPH。