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：
10652574
负责人：
Heather R Burkin
金额：
$ 32.18万
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/10652574
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 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 drug development druggable target enzyme activity experience experimental study health disparity human tissue improved inhibitor molecular drug target myometrium novel novel therapeutics perinatal health pharmacologic 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.

项目摘要基质金属蛋白酶2和金属蛋白酶9（MMP2/9）已显示在A中起活性作用各种细胞反应，包括子宫收缩的调节。基础分子驱动这些效果的机制目前尚不清楚。该提议的总体目的是了解 MMP9促进子宫收缩并确定MMP9的特定抑制的机制促进子宫静止。中心假设是MMP9升高到早产的水平患者足以增加人子宫组织的收缩反应并驱动早产。该提案将确定纯化的MMP9是否促进子宫收缩和MMP9的特定抑制促进子宫和早产子宫组织的子宫静止。实验将进行确定MMP9抑制是否会延迟早产动物模型中的分娩。最后，这个建议将确定MMP9抑制是否通过减少细胞内钙瞬变和应用蛋白质组学技术来识别MMP9作用的新型机制。这些数据预计将是重要的是因为它们将为将来的实验提供基础，以确定MMP9或相关途径抑制剂可以用作促进子宫静止并减少的可药靶标数字早产。