# Post-translational Modification of Cx43 Regulates Myometrial Quiescence

> **NIH NIH R21** · UNIVERSITY OF NEVADA RENO · 2024 · $183,750

## Abstract

PROJECT SUMMARY ABSTRACT
Preterm birth is a major medical problem resulting in disability and death for very preterm infants. Therapeutic approaches
to manage preterm labor are off-label and ineffective. No tocolytic therapy in use today is satisfactory beyond 48 hours, and
none are FDA approved. Preterm labor more often impacts African American women than their Caucasian counterparts.
We seek to understand the dysfunctional relaxation of the myometrium that leads to preterm labor and resulting preterm
birth. Our central hypothesis is that nitric oxide is generated locally within the myometrium by microvascular endothelial
cells as a result of mechanical stretch and increased blood flow to the expanding uterus. Nitric oxide S-nitrosates Cx43 in
the muscle cell. Cx43 S-nitrosation promotes C-terminal phosphorylation that holds Cx43 in its hemichannel state and
favors muscle cell quiescence. Hemichannels form gap junctions at the time of labor. Gap junctions are a feature of activated
myometrium. Promoting connexin 43 S-nitrosation offers a unique target for tocolytic development. Translational
approaches in human pregnancy tissues are essential if we are to discover and exploit the unique mechanisms that subserve
uterine quiescence during pregnancy and their dysregulation in preterm labor.

## Key facts

- **NIH application ID:** 10784717
- **Project number:** 5R21HD108728-02
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** IAIN L BUXTON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $183,750
- **Award type:** 5
- **Project period:** 2023-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784717

## Citation

> US National Institutes of Health, RePORTER application 10784717, Post-translational Modification of Cx43 Regulates Myometrial Quiescence (5R21HD108728-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10784717. Licensed CC0.

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