# Post-translational Modification of Cx43 Regulates Myometrial Quiescence

> **NIH NIH R21** · UNIVERSITY OF NEVADA RENO · 2024 · $57,310

## Abstract

PROJECT SUMMARY ABSTRACT
Women of color are underrepresented in biomedical research and this Diversity Supplement is submitted to
mentor Mariani Ramirez to earn a PhD as a pharmacologist. Her project is to look for ways to prevent preterm
birth, 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:** 10930410
- **Project number:** 3R21HD108728-02S1
- **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:** $57,310
- **Award type:** 3
- **Project period:** 2023-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930410

## Citation

> US National Institutes of Health, RePORTER application 10930410, Post-translational Modification of Cx43 Regulates Myometrial Quiescence (3R21HD108728-02S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10930410. Licensed CC0.

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