MMP9 Modulation of Uterine Contraction and Birth Timing

MMP9 对子宫收缩和出生时间的调节

基本信息

批准号：
10425356
负责人：
Heather R Burkin
金额：
$ 33.23万
依托单位：
UNIVERSITY OF NEVADA RENO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10425356
关键词：
Ablation Affect Amniotic Fluid Animal Model Automobile Driving Birth Birth Rate Calcium Calcium Signaling Data Event Foundations Future Gap Junctions Gelatinase A Goals Human Impairment Infant Infant Mortality Inflammatory Intervention MMP9 gene Metalloproteases Mission Modeling Molecular Molecular Target Mus National Institute of Child Health and Human Development Outcome Oxytocin Pathway interactions Patients Pharmacologic Substance Pharmacology Plasma Play Pregnancy Pregnancy Outcome Pregnant Uterus Premature Birth Premature Labor Process Production Proteomics Public Health Rattus Regulation Research Research Priority Role SB 3CT compound Serum Signal Pathway Signal Transduction Technology Testing Tissues United States Uterine Contraction Uterus Woman Yin base drug development druggable target enzyme activity experience experimental study health disparity human tissue improved inhibitor molecular drug target myometrium novel novel therapeutics perinatal health premature prevent response side effect

项目摘要

PROJECT SUMMARY Matrix Metalloproteinases 2 and Metalloproteinase 9 (MMP2/9) have been shown to play active roles in a variety of cellular responses, including the regulation of uterine contraction. The underlying molecular mechanisms driving these effects are currently unknown. The overall objective of this proposal is to understand the mechanisms by which MMP9 promotes uterine contraction and to determine if specific inhibition of MMP9 promotes uterine quiescence. The central hypothesis is that elevation of MMP9 to levels seen in preterm patients is sufficient to increase the contractile response in human uterine tissue and drive preterm parturition. This proposal will determine if purified MMP9 promotes uterine contraction and if specific inhibition of MMP9 promotes uterine quiescence in term and preterm human uterine tissue. Experiments will be performed to determine if MMP9 inhibition can delay parturition in preterm animal models. Finally, this proposal will determine if MMP9 inhibition promotes uterine quiescence by decreasing intracellular calcium transients and apply proteomic technologies to identify novel mechanisms of MMP9 action. These data are expected to be significant because these they will provide the foundation for future experiments to determine if MMP9 or related pathway inhibitors can serve as druggable targets to promote uterine quiescence and reduce the number preterm births.

项目概要基质金属蛋白酶 2 和金属蛋白酶 9 (MMP2/9) 已被证明在各种细胞反应，包括子宫收缩的调节。底层分子驱动这些效应的机制目前尚不清楚。该提案的总体目标是了解 MMP9 促进子宫收缩的机制并确定 MMP9 是否具有特异性抑制促进子宫安静。核心假设是 MMP9 升高至早产儿的水平足以增加人体子宫组织的收缩反应并促进早产。该提案将确定纯化的 MMP9 是否促进子宫收缩以及 MMP9 是否具有特异性抑制促进足月和早产人类子宫组织的子宫静止。将进行实验确定 MMP9 抑制是否可以延迟早产动物模型的分娩。最后，该提案将确定 MMP9 抑制是否通过减少细胞内钙瞬变促进子宫静止应用蛋白质组技术来确定 MMP9 作用的新机制。这些数据预计意义重大，因为它们将为未来的实验奠定基础，以确定 MMP9 或相关途径抑制剂可以作为药物靶点来促进子宫静止并减少子宫收缩早产数。