权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

MOLECULAR MECHANISMS OF CORPUS CAVERNOSUM FIBROSIS

海绵体纤维化的分子机制

基本信息

批准号：
2838141
负责人：
ROBERT B MORELAND
金额：
$ 11.67万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-12-20 至 2001-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2838141
关键词：
clinical research collagen connective tissue fibrosis forskolin human subject isoproterenol male molecular pathology nitroferricyanide penis penis erection prostaglandin E protein biosynthesis protein degradation smooth muscle tissue /cell culture transforming growth factors

项目摘要

DESCRIPTION (Adapted from the Applicant's Abstract): Erectile dysfunction occurs in varying degrees in 18 - 30 million American men. Recent therapeutic advances, have been based on research that elucidated the physiologic mechanisms of erectile tissue (e.g. trabecular smooth muscle) relaxation. The trabecular smooth muscle cell, which is intimately involved in contractility, also synthesizes connective tissue. They have shown that a critical ratio of trabecular smooth muscle to erectile tissue collagen is required for normal erectile function. They have further shown that elevated corporal connective tissue content impairs overall erectile tissue "expendability" during tumescence, interfering with sub-tunical venule occlusion, resulting in venous leakage. Vasculogenic impotence secondary to veno-occlusive dysfunction from structural changes is a common cause of erectile impairment and a major pathophysiology resulting in pharmacologic treatment failures and need for penile prosthesis insertion. One of the least studied aspects of erectile physiology is the mechanism(s) by which trabecular smooth muscle regulates connective tissue synthesis and degradation. Transforming growth factor-beta (TGF) is a pleiotropic cytokine which induces connective tissue synthesis and has been implicated in soft tissue fibrosis. They have shown that human corpus cavernosum expresses TGF. They have developed a human corpus cavernosum smooth muscle cell culture model which maintains functional and structural elements of connective tissue proteins. TGF induces collagen synthesis in this model. This synthesis was suppressed by prostaglandin E1, forskolin, isoproterenol and sodium nitroprusside, agents which elevate cyclic nucleotide levels. They propose to test if collagen synthesis and degradation in this model is regulated by substances which alter cyclic nucleotide levels. Using this model, they will: (1) investigate TGF- induced collagen synthesis and degradation, (2) determine the effects of cyclic nucleotide elevating agents on TGF-induced collagen synthesis and (3) investigate the effects of TGF and cyclic nucleotide elevating agents on TGF and PGE synthesis and expression of their receptors. Previous research on trabecular smooth muscle contractility has led to innovative therapeutic approaches to treat erectile dysfunction. It is anticipated that corporal collagen research will lead to novel pharmacologic prophylactic therapies to restore and/or preserve a functional trabecular smooth muscle content and maintain erectile potency.

描述（改编自申请人的摘要）：勃起功能障碍在1800万至3000万美国男性中不同程度地发生。最近治疗进展，一直是基于研究，阐明了勃起组织的生理机制（例如小梁平滑肌）放松. 小梁平滑肌细胞，它密切参与在收缩性，也合成结缔组织。他们发现小梁平滑肌与勃起组织胶原蛋白的临界比率是正常勃起功能所必需的他们进一步表明，升高的身体结缔组织含量损害整体勃起组织肿胀时的“扩张性”，干扰内膜下小静脉闭塞，导致静脉渗漏。血管性阳痿继发于结构变化引起的静脉闭塞功能障碍是勃起障碍和导致药理学的主要病理生理学治疗失败和需要阴茎假体插入。之一勃起生理学研究最少的方面是机制，小梁平滑肌调节结缔组织合成，降解转化生长因子-β（TGF）是一种多效性的诱导结缔组织合成的细胞因子软组织纤维化他们发现人类阴茎海绵体表达TGF。他们已经开发出一种人类阴茎海绵体平滑肌细胞培养模型，该模型保持了结缔组织蛋白 TGF在该模型中诱导胶原合成。这种合成被前列腺素E1、毛喉素、异丙肾上腺素抑制和硝普钠，它们是提高环核苷酸水平的药剂。他们建议测试在这个模型中胶原蛋白的合成和降解是否由改变环核苷酸水平的物质调节。使用此模型，他们将：（1）研究TGF-诱导的胶原合成，降解，（2）确定环核苷酸提升剂的作用对TGF-诱导的胶原合成的影响;（3）研究TGF和环核苷酸升高剂对TGF和PGE合成和表达的影响它们的受体。小梁平滑肌的既往研究收缩性导致了治疗勃起障碍的创新治疗方法功能障碍预计身体胶原蛋白的研究将导致用于恢复和/或保持一种或多种免疫缺陷的新的药理学预防性疗法，功能性小梁平滑肌含量和维持勃起能力。