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Real Time Imaging of Urinary Tract Smooth Muscle Function

尿路平滑肌功能实时成像

基本信息

批准号：
8879130
负责人：
DORIS A HERZLINGER
金额：
$ 33.9万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8879130
关键词：
Automobile Driving Benign Biological Models Bladder Cations Child Collaborations Complex Defect Development Diagnosis Distal End stage renal failure Exhibits Functional Imaging Functional disorder Genetic Genitourinary system Human Hydronephrosis Imaging Techniques Interdisciplinary Study Kidney Kidney Failure Lead Lower urinary tract Maps Microscopic Molecular Mus Muscle function Mutant Strains Mice Optics Pathway interactions Pattern Peristalsis Pharmacotherapy Physiological Physiology Play Process Protocols documentation Research Infrastructure Resource Development Resources Role Smooth Muscle Structure System Systems Analysis Systems Development Techniques Time Tissues Ureter Urethra Urinary tract Urologic Diseases Urologist Urology base drug testing experience imaging modality insight medical schools mutant mouse model nodal myocyte novel novel strategies programs public health relevance tool urinary tract imaging urinary tract motility urologic wasting

项目摘要

DESCRIPTION (provided by applicant): Lower urinary tract (LUT) dysfunction is the most common cause of end-stage renal disease in children. Although several genetic pathways controlling LUT structure have been identified, the genetic pathways controlling the coordinated contraction of LUT musculature, a process essential for moving wastes out of the body, remain poorly understood. This is due, in large part, to the absence of techniques to assess LUT motility in real time in intact tissues such as the ureter, bladder and urethra. We have developed a novel ureter explant system and video microscopic and optical mapping protocols to analyze ureteral smooth muscle contractile and excitation patterns and discovered that the initiation of electrical activity driving coordinated, proximal to distal contraction is dependent on pacemaker cells that express hyperpolization activated cation channels. This Resource Center will apply our state-of-the-art functional imaging techniques to existing mouse mutants exhibiting LUT dysfunction to determine if aberrant smooth muscle function plays a causative, pathological role. Results of these studies will provide much needed model systems to identify the molecular mechanisms underlying coordinated LUT motility and ultimately yield novel drug therapies to treat inborn or acquired defects in this process.

描述（由申请人提供）：下尿路（LUT）功能障碍是儿童终末期肾病的最常见原因。虽然已经确定了几种控制LUT结构的遗传途径，但控制LUT肌肉组织协调收缩的遗传途径仍然知之甚少，这是将废物排出体外所必需的过程。这在很大程度上是由于缺乏在完整组织如输尿管、膀胱和尿道中真实的时间评估LUT运动性的技术。我们已经开发了一种新的输尿管移植系统和视频显微镜和光学映射协议来分析输尿管平滑肌收缩和兴奋模式，并发现启动电活动驱动协调，近端到远端收缩依赖于起搏细胞，表达超极化激活阳离子通道。该资源中心将把我们最先进的功能成像技术应用于现有的表现出LUT功能障碍的小鼠突变体，以确定异常的平滑肌功能是否发挥致病性、病理性作用。这些研究的结果将提供急需的模型系统，以确定协调LUT运动的分子机制，并最终产生新的药物治疗，以治疗先天性或后天性缺陷，在这个过程中。