# Fate of the kidney vasculature during partial neonatal ureteral obstruction

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $363,375

## Abstract

ABSTRACT
Obstructive nephropathy, the leading cause of chronic kidney disease in infants and children not only impairs
nephrogenesis but can also lead to progressive destruction of immature and mature nephrons via injury to the
vascular, tubular, and interstitial compartments. The proposed research project is designed to identify the
vascular precursors and the mechanisms whereby they repair the injured kidney, using a model of reversible
partial unilateral ureteral obstruction (pUUO) in the neonatal mouse, which parallels urinary tract obstruction in
the human fetus. Our preliminary data using genetic cell fate tracing techniques show that during neonatal
pUUO there are severe abnormalities in the renal arterial tree followed by loss of proximal tubular and
collecting duct cells. Concomitant with the nephrovascular damage, there is expansion of interstitial cells
ultimately leading to fibrosis. Remarkably, upon release of obstruction, reversal of the damage occurs with
regeneration of the vasculature, proximal tubules and collecting ducts. The striking recovery observed after
release of ureteral obstruction requires the reenactment of developmental pathways that control cell fate,
positional information and organized growth. We propose that the kidney vasculature plays a direct and
central role in the ability of the kidney to regenerate and repair after injury. Therefore, in this proposal we
will test the interrelated hypotheses that ureteral obstruction leads to defective vascular morphogenesis and
changes in cell fate and that that RBP-J (the transcriptional effector of all the Notch receptors) not only controls
the normal development of the kidney vessels, but also the fate and regeneration of the vasculature and its
associated nephrons after release of obstruction. In summary, we will explore how changes in cell identity and
fate create massive morphological and functional changes which in turn determine whether the tissue will be
healthy or unrecoverable. Specific Aim 1 will define the vascular changes of the postnatal kidney following
obstructive nephropathy and after release, Specific Aim 2 will determine the fate of vascular cells using
specific Cre recombinant and fluorescent reporter mouse lines, and Specific Aim 3 will determine whether
Rbp-J plays a role in the regeneration and maintenance of the renal vasculature and associated nephrons
during obstruction and after its release using mice with inducible expression of Cre recombinase and
concomitant fluorescent reporter expression that allows to trace the fate of the mutant cells. The proposed
work will fill an important gap in our knowledge: deciphering the cellular and molecular mechanisms involved in
nephrovascular repair and regeneration has potential therapeutic implications for infants and children and the
growing adult population suffering from chronic kidney disease.

## Key facts

- **NIH application ID:** 10159245
- **Project number:** 5R01DK116196-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** MARIA LUISA Soledad SEQUEIRA-LOPEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $363,375
- **Award type:** 5
- **Project period:** 2018-07-20 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159245

## Citation

> US National Institutes of Health, RePORTER application 10159245, Fate of the kidney vasculature during partial neonatal ureteral obstruction (5R01DK116196-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159245. Licensed CC0.

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