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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：
10237117
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/10237117
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/antagonist 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.

项目总结基质金属蛋白酶2和金属蛋白酶9(MMP2/9)在肝细胞癌中发挥着积极作用。细胞反应的多样性，包括子宫收缩的调节。潜在的分子驱动这些效应的机制目前尚不清楚。这项建议的总体目标是理解 MMP9促进子宫收缩的机制及MMP9的特异性抑制促进子宫平静。中心假设是MMP9升高到早产时的水平患者的子宫收缩反应足以增加人类子宫组织的收缩反应，并促使早产。这项提议将确定纯化的MMP9是否促进子宫收缩，以及是否特异性抑制MMP9 促进足月儿和早产儿子宫组织中的子宫静止。将进行实验，以在早产动物模型中确定抑制MMP9是否可以推迟分娩。最后，这项提议将确定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确定MMP9作用的新机制。这些数据预计将是意义重大，因为它们将为未来的实验提供基础，以确定MMP9或相关途径抑制物可作为促进子宫静息和减少子宫出血的药物靶点。早产儿数量。