# Targeting Microvesicles in Kidney Disease

> **NIH NIH R21** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $195,625

## Abstract

PROJECT SUMMARY
Extracellular vesicles (EV) transport and deliver signaling molecules to distant cells to support metabolic
processes, kidney development and homeostasis. Deregulation of EV signals are associated with metabolic and
chronic kidney disease. EV cargo inhibit glucose transporters, leading to insulin resistance. In addition, EV
stimulate profibrotic factors to drive kidney fibrosis in diabetic patients. Furthermore, EV are implicated in the
pathogenesis of polycystic kidney disease. Despite the growing realization that EV play a vital role in kidney
disease, our basic knowledge of the molecular principles that control EV formation and cargo loading remains
fundamentally limited.
Identifying and targeting molecules that control EV biogenesis in predictive animal models has the potential to
lead to novel and synergizing therapeutics for the benefit of kidney disease patients.
EV release is an evolutionary conserved process from algae to flies to humans, suggesting that broadly
generalizable molecular requirements for this process exist. Drosophila melanogaster has been invaluable in the
discovery of conserved signaling dynamics relevant to human diseases, including nephropathies. To begin to
explore the molecular mechanism of EV release and cargo loading, we have developed an in vivo EV labeling
system in Drosophila epithelial tissues. This system permits the visualization of EV secretion steps in live imaging
approaches. Importantly, we have adapted this system for EV proteomic studies aimed at identifying novel
regulators of EV biogenesis and cargo loading. Further, the system is amenable to targeted genetic mutant
analyses, permitting robust functional validation of putative EV regulators. In this exploratory R21 grant, we are
proposing to use our systems to identify novel EV regulators. Validated regulators will form the basis of a follow-
up R01 grant focused on delineating the underlying mechanisms using tissue culture and murine models of
chronic kidney disease.

## Key facts

- **NIH application ID:** 10442677
- **Project number:** 5R21DK129899-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Chiswili Yves Chabu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,625
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442677

## Citation

> US National Institutes of Health, RePORTER application 10442677, Targeting Microvesicles in Kidney Disease (5R21DK129899-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10442677. Licensed CC0.

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