# Plasminogen in glomerular disease progression

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $533,918

## Abstract

Project Summary
Primary and secondary pathogenic processes affecting glomerular podocytes contribute significantly to the
burden of end-stage renal disease (ESRD). Despite significant evidence identifying the podocyte as the key
glomerular cell target for injury, validated therapeutic targets are scarce and commercially available cell-specific
therapy is lacking. Our long-term goal is to identify key regulatory pathways and therapeutic targets in the
treatment of glomerular disease. Our work has identified the urinary serine protease plasminogen as a mediator
of podocyte injury and a targetable biomarker that correlates with albuminuria and renal function. The overall
objective of this application is to define the role of plasminogen as a “second hit” mediator of podocyte injury and
a potential therapeutic target in progressive glomerular disease. Our central hypothesis is that under normal
conditions with an intact glomerular filtration barrier, podocytes are not exposed to plasminogen. In proteinuric
disease, plasminogen enhances podocyte injury through urokinase type plasminogen activator as part of a
second hit with plasminogenuria correlating with the risk of glomerular disease progression . The rationale for
the proposed research is that characterizing the role of plasminogen in podocyte injury and glomerular disease
progression could define it as a targetable biomarker in the treatment of proteinuric kidney disease. Our
hypothesis will be tested by pursuing two specific aims: Aim 1 will define the role of plasminogen in podocyte
injury and glomerular disease. We will define the mechanism by which plasminogen induces podocyte injury,
test the role of podocyte plasminogen activator inhibitor 1 in glomerular disease progression and leverage the
CureGN cohort to define the relationship between urinary plasminogen and human glomerular disease
progression. In Aim 2 we will test plasminogen inhibition as a therapeutic strategy in proteinuric kidney disease
using genetic models as well as novel pharmacologic compounds targeting plasminogen activation. Our
innovative approach utilizes state of the art cell and molecular biology, biomarker analysis, imaging, systems
biology and medicinal chemistry tools to define plasminogen as a mediator of glomerular disease progression.
These contributions are significant because they are part of a continuum of research that is expected to advance
understanding of glomerular disease progression and identify therapeutic targets and strategies to improve
clinical outcomes.

## Key facts

- **NIH application ID:** 10072973
- **Project number:** 1R01DK126477-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Kirk N Campbell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $533,918
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072973

## Citation

> US National Institutes of Health, RePORTER application 10072973, Plasminogen in glomerular disease progression (1R01DK126477-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072973. Licensed CC0.

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