# The role of ICOSL in renal protection

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $366,287

## Abstract

Project Summary/Abstract
Glomerular injury leads to proteinuric kidney diseases that often progress to renal failure. Despite advances in
our understanding of the pathogenesis of glomerular disease, current treatment relies heavily on
immunosuppressive or anti-hypertensive drugs and specific treatments are still lacking. Regardless of the
underlying cause, one early and unifying event in glomerular injury is a morphological change in podocytes
called foot process (FP) effacement. Activation of αvβ3 integrin on podocytes is linked to early pathological
processes leading to FP effacement and the subsequent induction of proteinuria in several glomerular
diseases, including FSGS and DN. Conversely, blocking of αvβ3 activation significantly reduces proteinuria
and subsequent disease progression in animal models of FSGS and DN. However, there is currently no
clinically successful approach designed to target αvβ3 integrin.
 We recently discovered a novel role for inducible co-stimulator ligand (ICOSL) in the protection against
early glomerular injury (Koh et al., JCI, 2019). Glomerular ICOSL expression increases in early stages of
human FSGS and DN, followed by a drastic decline at later stages. ICOSL deficient animals are more
susceptible to kidney injury and severe proteinuria, and can be rescued by recombinant ICOSL injection.
ICOSL’s RGD motif is critically important for binding to activated αvβ3 as well as its protective function. Despite
this important discovery that ICOSL contributes to kidney protection, more detailed mechanistic studies are
necessary to fully understand the renoprotective behavior of ICOSL as a regulator of αvβ3 integrin and to
develop targeted therapies.
 Based on our published and preliminary data, we hypothesize that elevated ICOSL expression is a
mechanism launched by podocytes as an endogenous defensive response to limit progressive kidney injury by
counterbalancing the harmfully excessive activation of αvβ3 integrin. To test this hypothesis, we will precisely
define the essential temporal and spatial regulation of ICOSL expression necessary to deploy its protective
action (Aim 1), determine how ICOSL achieves renoprotection (Aim 2), and explore its therapeutic potential
(Aim 3). Our studies will be essential steps in moving toward successful development of novel specific
therapeutics for αvβ3 integrin-mediated glomerular diseases.

## Key facts

- **NIH application ID:** 10209294
- **Project number:** 1R01DK125394-01A1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Eunsil Hahm
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $366,287
- **Award type:** 1
- **Project period:** 2021-03-08 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209294

## Citation

> US National Institutes of Health, RePORTER application 10209294, The role of ICOSL in renal protection (1R01DK125394-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10209294. Licensed CC0.

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