# suPAR and renal fibrosis

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $422,302

## Abstract

Abstract
Chronic kidney disease (CKD) is a major driver of mortality and a financial challenge for healthcare in
the United States. Treatment options are scarce, indirect and not sufficient, whilst CKD is growing into
one of the largest unmet medical needs of our time.
Once the kidney is injured, progression of the disease is dependent on the degree of fibrosis, which
can differ from patient to patient. We and others have made the unique observation that the soluble
form of urokinase plasminogen activator receptor (uPAR) is a risk factor for incident and prevalent
kidney diseases across the spectrum of CKD. suPAR is a three finger toxin that is produced by
immature myeloid cells in the bone marrow and circulates in the plasma to regulate integrin function
in the kidney. Elevated suPAR levels or the presence of certain suPAR isoforms are causally
involved in CKD by mediating injury to both glomerular podocytes and proximal tubular cells through
specific interactions with β integrins. Building on our published and novel preliminary observations
that suPAR-mediated integrin activation drives fibrotic programs in the kidney, we plan to investigate
the consequences of suPAR interactions with distinct β integrins in different nephron segments and
explore its role in promoting both glomerular and tubulointerstitial fibrosis. Three independent aims
are being proposed: First, we will determine the molecular mechanisms that translate suPAR-αvβ3
integrin signaling into podocyte injuries and glomerular sclerosis using surface plasmon resonance
assays, cultured cell experiments and suPAR transgenic mouse models. Second, we will determine
the molecular mechanisms that drive suPAR-αvβ6 integrin signaling in tubular injuries and
tubulointerstitial fibrosis by genetically modifying the tubular integrin function. Third, we will
investigate therapeutic modalities using peptide based blocking strategies for uPAR and its
associated fibrotic pathways. Experiments outlined in this proposal will allow us to separate different
steps in the suPAR cascade of kidney fibrosis and define best options to intervene. As such, insights
from this grant will provide a basis for preventive and treatment strategies to combat suPAR mediated
fibrosis and CKD.

## Key facts

- **NIH application ID:** 10829902
- **Project number:** 5R01DK125858-06
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** David Changli WEI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $422,302
- **Award type:** 5
- **Project period:** 2020-07-20 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829902

## Citation

> US National Institutes of Health, RePORTER application 10829902, suPAR and renal fibrosis (5R01DK125858-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10829902. Licensed CC0.

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