MMP9 Modulation of Uterine Contraction and Birth Timing

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Heather R Burkin
Organization: UNIVERSITY OF NEVADA RENO
Fiscal Year: 2024
Award: $4,229
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development

PROJECT SUMMARY
 Matrix Metalloproteinases 2 and Metalloproteinase 9 (MMP2/9) 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 the parent 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. The parent project
includes experiments will be performed to determine if MMP9 inhibition can delay parturition in preterm mouse
models. This supplemental project will enhance the parent proposal by identifying genes and proteins whose
uterine expression is altered when MMP activity is systemically blocked. These data are expected to be
significant because these they will identify potential mechanistic links to explain how MMP2/9 modulate uterine
contractions. These data will provide a foundation for future experiments to determine if MMP2/9 substrates
can serve as druggable targets to promote uterine quiescence and reduce the number preterm births.

Terms: <72-kDa Gelatinase><72-kDa Type IV Collagenase><72kD type IV Collagenase><Automobile Driving><Birth><Body Tissues><CLG4B><Data><Foundations><Future><GELB><Gelatinase A><Gelatinase Neutrophil><Genes><Human><Infant Mortality><Infant Mortality Total><Link><MMP-2><MMP9><MMP9 gene><MMPs><Matrix Metalloproteinase-2><Matrix Metalloproteinases><Metallopeptidases><Metalloproteases><Metalloproteinases><Mission><Modern Man><Molecular><Myometrial Contraction><NICHD><National Institute of Child Health and Human Development><National Institute of Children's Health and Human Development><Parents><Parturition><Patients><Play><Premature Birth><Prematurely delivering><Preterm Birth><Proteins><Public Health><Regulation><Role><Tissues><United States><Uterine Contraction><Uterus><death among infants><death in first year of life><death in infancy><death in infants><driving><druggable target><experiment><experimental research><experimental study><experiments><infant death><infant demise><infantile death><mortality in infants><mouse model><murine model><parent><parent award><parent project><premature childbirth><premature delivery><preterm delivery><response><social role><womb>