Role of Tamm-Horsfall Protein in Urinary Track Infection

Tamm-Horsfall 蛋白在尿路感染中的作用

基本信息

批准号：
7347040
负责人：
SATISH KUMAR
金额：
$ 28.58万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2010-07-31
项目状态：
已结题

项目摘要

Tamm-Horsfali protein(THP) is urine's most abundant protein. Its function has remained unclear, despite extensive research for over a century. One of the hypotheses about its function has been that it acts as a host defense actor against urinary tract infection. We are one of two groups to createthe first gene knockout mousefor THP. n PRELIMINARY STUDIES, THP-deficient mice have difficulty clearing bacteria from the urinary bladder. The SPECIFIC AIMS of this proposalare: A1M#1) To define and circumscribe the role of THP as a host defensefactor against UTI a) To determine if THP (-/-) mice are more proneto cystitis (inflammation of urinary bladder) in comparison with THP (+/+) mice, after transurethralinoculation of E.coli. b) To determine if THP (-/-) mice are more prone to pyelonephritis (inflammation of kidneys) in comparison with THP (+/+) mice, after transurethral inoculation of E.coli. c) To determine if the severity of bladder and kidney infection in THP (-/-) mice is related to the specific type of fimbrial expression in E. coll. ', d) To determine if THP (-/-) mice are more prone to UTI with bacteria other than E co//r specifically Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Enterococcus fecaelis and Morganella morganii, as measured by bladder and kidney bacterial loads after transurethral inoculation. AIM#2) To determine the mechanism of THP affecting the susceptibility for UTI a) Effect of THP on bacterial clearance from bladder . b) Effect of THPon bacterial - urothelial cell interaction c) Effectof THP on bacterial-leukocyte interaction SIGNIFICANCE: These studies will clarify the function of urine's most abundant protein and will providenew knowledge about a host defense mechanism against UTI. The findings will allow a better understanding of the pathogenesis of UTI, a commonhuman illness.

Tamm-Horsfali蛋白（THP）是尿液最丰富的蛋白质。尽管一个多世纪的广泛研究。关于其功能的假设之一是它充当宿主防御反对尿路感染的演员。我们是创建第一个基因敲除小鼠THP的两个组之一。 N初步研究，THP缺陷小鼠很难从膀胱中清除细菌。此提案的具体目的： A1M＃1）定义和限制THP作为对UTI的宿主防御法的作用 a）确定THP（ - / - ）小鼠是否是膀胱炎（膀胱炎症）在E.coli进行了尿道氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基氨基苯甲酸后的比较。 b）确定THP（ - / - ）小鼠是否更容易发生肾盂肾炎（肾脏的炎症）在尿道接种大肠杆菌后，与THP（+/+）小鼠进行了比较。 c）确定THP（ - / - ）小鼠中膀胱和肾脏感染的严重程度是否与特定有关 E. coll中的纤维化表达的类型。 '，d）确定thp（ - / - ）小鼠是否更容易使用ECO // r以外的细菌特定于肺炎的克雷伯菌，proteus mirabilis，pseudomonas铜绿疾病，葡萄球菌，葡萄球菌，肠球菌Fecaelis和Morganella Morganii，作为经尿道接种后通过膀胱和肾脏细菌负荷测量。目标＃2）确定影响UTI易感性的THP机制 a）THP对膀胱细菌清除的影响。 b）Thpon细菌 - 尿路上皮细胞相互作用的影响 c）THP对细菌 - 白细胞相互作用的影响意义：这些研究将阐明尿液最丰富的蛋白质的功能，并将在Providenew 关于针对UTI的宿主防御机制的知识。这些发现将使对 UTI的发病机理，一种常见的人类疾病。