# The role of HGFL in the sickle cell disease nephropathy

> **NIH NIH SC1** · HOWARD UNIVERSITY · 2020 · $386,250

## Abstract

Sickle cell disease (SCD) is caused by a single nucleotide mutation in the β-globin gene resulting in the
polymerization of hemoglobin (HbS) in red blood cells (RBCs) under low oxygen conditions leading to
hemolysis and vaso-occlusion. SCD is the most common hereditary disorder which affects approximately
100,000 people in the USA, primarily of African descent. Renal complications are the most common
complications in SCD patients. They range from various tubular and glomerular functional abnormalities to
gross anatomic alterations of the kidney. Overall, SCD patients have an approximately three-fold higher risk to
develop chronic kidney disease (CKD) than the general population. More than 50% of SCD patients develop
CKD in association with comorbidities and early mortality. However, the current standards of diagnosis and
care can only delay progression of this disease. This is due to a lack of effective therapies and an absence of
reliable assays for diagnosis of the early disease, before renal damage is severe or irreversible. New
diagnostic and therapeutic tools are urgently needed. Development of these tools requires an improved
understanding of the disease mechanism and identification of new biomarkers of disease onset and
progression. The majority of renal complications of SCD result from functional vasculopathy and endothelial
injury. In contrast, the key event in the development of glomerular complications leading to CKD is podocyte
injury. This highlights a major gap in our knowledge of the mechanism of glomerular disease development in
SCD. This proposal lays out a sophisticated approach to validate the role of hepatocyte growth factor like
(HGFL) protein in the development of CKD in SCD. We hypothesize that RBC hemolysis products activate
protease in infiltrated renal macrophages inducing a cascade of circulating HGFL activation and glomerular
endothelial and epithelial cell injury. In Aim 1, macrophage activation by the products of sickle RBC hemolysis
and its role in the development of glomerular injury will be studied. In Aim 2, the role of HGFL and its receptor,
RON, in the induction of glomerular podocytes injury will be evaluated. In Aim 3, target-specific quantitative
assays, e.g. ELISA and single reaction monitoring mass-spectrometry will be used to validate correlation of
urinary HGFL levels with estimated glomerular filtration rates (eGFR) in case-control study using Howard
University Center for Sickle Cell Disease repository samples. This proposal is designed to evaluate the role of
HGFL in the development of glomerular injury in SCD and validate HGFL as a novel diagnostic tool for
hyperfiltration detection. A faculty research enhancement plan includes a strategy that will lead to developing
an independently-funded basic and translational research program in SCD renal disease.

## Key facts

- **NIH application ID:** 10021022
- **Project number:** 5SC1HL150685-02
- **Recipient organization:** HOWARD UNIVERSITY
- **Principal Investigator:** MARINA A JEREBTSOVA
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2019-09-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021022

## Citation

> US National Institutes of Health, RePORTER application 10021022, The role of HGFL in the sickle cell disease nephropathy (5SC1HL150685-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10021022. Licensed CC0.

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