# lntegrin binding proteins and the kidney

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

A hallmark of chronic kidney disease (CKD) is advancing tubulointerstitial (TI) fibrosis. While new mechanisms
of fibrosis have been uncovered in recent decades, effective treatment to directly halt or reverse this process
remains elusive. Our group has a long-standing interest in defining how extracellular matrix (ECM) receptors
such as integrins and their binding partners regulate kidney development and response to injury. Among the
integrin binding partners, we focus on the integrin linked kinase (ILK); pinch; α-parvin complex of scaffold
proteins, also known as the IPP complex. We recently uncovered a novel modality to interfere with integrin
dependent signaling pathways mediated by the IPP complex that may represent a new strategy to treat and
prevent TI fibrosis and ultimately CKD.
Integrins are transmembrane receptors composed of non-covalently bound α and β subunits. β1 is the most
abundantly expressed subunit in the kidney and can bind 12 different α subunits. The β1 cytoplasmic tail
functions by binding multiple cytoplasmic proteins which regulate integrin-mediated signaling and cytoskeleton
modulation. The IPP complex is a major scaffolding hub that binds the integrin β1 cytoplasmic tail and its key
function is to bundle actin filaments, thereby transmitting mechanical signals between integrins and the actin
cytoskeleton. A normal actin cytoskeleton is required for most cell functions necessary for embryonic
development and recovery of tissue from injury. ILK is the major scaffold protein that brings the IPP complex
together; however, the α and β parvins are the major IPP complex proteins that regulate the actin cytoskeleton.
We have preliminary evidence that α-parvin is required for normal kidney development and repair after injury.
Deletion of α-parvin in mice at the initiation of the kidney collecting system (E10.5) causes severely dysmorphic
kidneys with excessive basolateral F-actin. We also provide evidence that deleting α-parvin in the fully developed
kidney collecting system (E 18.5) results in excessive tubular injury following a unilateral ureteric obstruction
(UUO) model. Mice carrying a mutant ILK unable to bind to α-parvin (K-to-M mutation in a.a. 220: ILK-K220M
mice) in the developing collecting system develop normally and wild-type mice treated with the small molecule
Csbl-1 (that interferes with the ILK-α-parvin interaction) have decreased renal fibrosis following UUO. These
data strongly suggest that α-parvin performs multiple cellular functions that are independent of its interactions
with ILK and paradoxically disrupting ILK binding to α-parvin improves the response of the kidney to injury.
Finally, we have evidence that α-parvin-null collecting duct (CD) cells have excessive F-actin formation,
increased cell adhesion, spreading and migration as well as a profound increase in activated RhoA and Cdc42.
Based on these data, we hypothesize that α-parvin-mediated regulation of actin dynamics via Rho-GTPase
signaling prom...

## Key facts

- **NIH application ID:** 10866341
- **Project number:** 5I01BX002196-10
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** ROY ZENT
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-04-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866341

## Citation

> US National Institutes of Health, RePORTER application 10866341, lntegrin binding proteins and the kidney (5I01BX002196-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10866341. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*