# Understanding the Function of Tamm-Horsfall Protein in Acute kidney Injury.

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $355,255

## Abstract

Acute kidney injury (AKI) is a major determinant of mortality and morbidity in hospitalized patients.
Understanding the pathophysiology of AKI is essential for the development of therapy. This application
proposes to study the role of Tamm-Horsfall protein (THP) in AKI. This protein is expressed exclusively in the
kidney by cells of the thick ascending limbs (TAL) of Henle. In the last few years, we uncovered a key role of
THP in mediating a protective tubular cross-talk in AKI. We showed that THP regulates inflammatory signaling
and injury to S3 segments, which are neighboring tubules to TAL in the kidney outer medulla. The immediate
goal of the current proposal is to study the importance of the interaction of THP with S3 segments in regulating
neutrophil infiltration and limiting oxidative stress in AKI. These studies will form the basis to transition into
therapeutic applications. Indeed, the PI's long term goal is to understand how the role of THP can be
modulated to treat patients who develop AKI.
The central hypothesis is that Tamm-Horsfall protein regulates the inflammatory response triggered by
ischemic injury in the outer medulla; an effect that requires an interaction of THP with the surrounding tubular
elements. This hypothesis has been formulated on the basis of strong preliminary and published data. The
following specific aims will be used to investigate this hypothesis.
Aim 1 will investigate the role of THP as a key regulator of neutrophil infiltration in the kidney after AKI.
Aim 2 will study the functional significance of the interaction of THP with neighboring epithelium in kidney
injury
Aim 2 will investigate therapeutic modulation of THP to inhibit neutrophil influx and promote recovery after AKI
This research will involve the use of THP knockout and wild type mice. The animal model used for AKI is renal
ischemia-reperfusion injury achieved through renal pedicle clamping. In vitro studies will involve cell lines for
proximal tubules. Other techniques used in this work include: Immunofluorescence laser micro-dissection of
specific tubular sections, Immunofluoresence confocal and intravital microscopy, flow cytometry, real time-
PCR, western blot, various forms of chromatography and mass spectrometry.
This research is innovative, because it will uncover novel regulatory functions for THP that may be relevant not
only in kidney injury but also in other forms of acute or chronic renal disease. Future strategies that enhance
the role of THP in the kidney will be of important therapeutic significance.

## Key facts

- **NIH application ID:** 10160893
- **Project number:** 5R01DK111651-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Tarek Maurice Ashkar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,255
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160893

## Citation

> US National Institutes of Health, RePORTER application 10160893, Understanding the Function of Tamm-Horsfall Protein in Acute kidney Injury. (5R01DK111651-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10160893. Licensed CC0.

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