# Role of nonmuscle myosin IIA in sex-dependent failed repair mechanisms in acute kidney injury

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2021 · $68,694

## Abstract

ABSTRACT
The cellular mechanisms that drive the progression of acute kidney injury (AKI) to chronic kidney disease (CKD)
are not well understood. AKI is the abrupt decrease of kidney function from a variety of causes that elicits
structural and functional damage. The prevalence of AKI is increasing rapidly in the United States and presents
a healthcare burden worldwide. To date, there are no effective therapies for the mitigation of the proinflammatory
and fibrotic phenotypes resulting from injury. Interestingly, it has been recently supported with epidemiological
data that female sex is a protective factor in the AKI progression to CKD. Leveraging the comparison of sex
specific mechanisms in ischemic injury has incredible potential for the identification of novel, effective therapeutic
targets. Therefore, I will be employing single nuclei RNA and ATAC-Sequencing, as well as spatial
transcriptomics to generate a multimodal atlas of the injury time course in females undergoing bilateral ischemia
reperfusion injury (Bi-IRI). Recently, a novel cell state has been identified in male mice following Bi-IRI using
single nuclei RNA sequencing. Known as failed repair proximal tubule cells (FR-PTC), these cells represent a
dead end in the recovery pathway and could be lending a role to increases in proliferation, fibrosis, and
inflammation that worsen kidney tissue after injury. These FR-PTCs exhibit a profile of differentially expressed
genes that are unique from healthy and repairing cell states. One of these genetic markers, which is also a
genome wide association study (GWAS) gene associated with CKD, was Myh9. Myh9 expression is upregulated
specifically in injured and failed repair cell clusters, and is found in low levels in healthy and repairing proximal
tubule cells. This gene encodes for nonmuscle myosin IIA (NMIIA), which plays an important role in cell shape,
adhesion, migration, and cytokinesis. It interacts directly with actin, creating a stable cytoskeletal network. Drastic
changes in Myh9 expression may translate into changes in NMIIA abundance that could alter the regulation of
downstream signaling, contributing to phenotypes characteristic of AKI. Therefore, I hypothesize that sexually
dimorphic expression of Myh9 in the kidney and sex-specific mechanisms of NMIIA activation contribute to the
renoprotection of female sex. Preliminary data suggests that female C57BL/6J mice at baseline have higher
expression of Myh9 than males, potentially indicating that females have developed mechanisms for decreasing
activity of NMIIA through downregulation of ischemia responsive kinases. This proposal will investigate these
expression changes in males and females along the injury time course following Bi-IRI using single nuclei
sequencing and spatial transcriptomics. Additionally, the relationship between ischemia and NMIIA function will
be investigated using gold standard biochemical techniques in in vivo and in vitro cell models. Ultimately, this
prop...

## Key facts

- **NIH application ID:** 10311908
- **Project number:** 1F32DK130249-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Eryn E. Dixon
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,694
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311908

## Citation

> US National Institutes of Health, RePORTER application 10311908, Role of nonmuscle myosin IIA in sex-dependent failed repair mechanisms in acute kidney injury (1F32DK130249-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10311908. Licensed CC0.

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