PROSTATIC SMOOTH MUSCLE GENE EXPRESSION

前列腺平滑肌基因表达

• 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
• 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

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)是增生性间质的主要成分。 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 受阿尔法肾上腺素能信号和雄激素信号的调节。鉴于已知的 雄激素和交感神经支配在老年高血压中的重要性 前列腺增生症的病理生理学，这些调节信号的潜在作用 在前列腺里是很明显的。不幸的是，前列腺的平滑肌 在最近的前列腺细胞和前列腺癌的研究中，细胞基本上被忽视了。 分子生物学。我们建议刻画一个表达式的 前列腺平滑肌细胞中重要的收缩蛋白-肌球蛋白 重链(MHC)，并确定雄激素和α肾上腺素能 信号调节表达。此外，前列腺ECM将被 具有蛋白质生化水平的特征和类似的调控 所研究的问题。蛋白质生化、免疫组织化学和分子生物学 生物技术将被用来解决以下具体问题 AIMS；1)人平滑肌MHC的克隆；2)MHC的发展 用于免疫印迹和免疫组织化学分析的单特异性抗体， 3)MHC在前列腺中的表达特征，4) 非肌肉型MHC在前列腺中的表达特征，5) α-氨基丁酸对人前列腺MHC和ECM表达的调节 肾上腺素能和雄激素信号，以及6)特征和调节 细胞外基质的表达。这些研究应该会提供重要的新见解 前列腺平滑肌细胞在病理生理学中的作用 良性前列腺增生症。