# Intracellular complement activation in Lupus Nephritis Podocytes

> **NIH NIH R21** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $218,750

## Abstract

Project Summary
Deposition of immune complexes and activation of the complement system mediates glomerular injury and is
involved in the inflammatory process in patients with lupus nephritis. Podocytes are highly specialized
epithelial cells which are critical for the proper function of the glomerular filtration barrier and are injured in
several proteinuric kidney diseases. Podocytes produce a number of complement factors and cathepsin
proteases. Preliminary evidence suggests that podocytes exposed to IgG form patients with lupus nephritis
produce increased amounts of complement which becomes activated intracellularly. We hypothesize that
exposure of podocytes to IgG from patients with lupus nephritis or to hypoxia promotes the production and
activation of complement intracellularly. We propose to identify complement components that are produced
by podocytes after exposure to IgG from patients with lupus nephritis or hypoxia. Next, we will determine how
cathepsin proteases activate complement intracellularly. For our studies we will use IgG from patients with
lupus nephritis, a newly establish method to culture podocytes on surfaces coated with decellularized
fibroblasts and podocytes from lupus-prone and cathepsin-deficient mice. CRISPR/Cas9 system will be
utilized to knockdown C3 and cathepsins (B, L and S) in podocytes. The studies will produce a novel concept
that intracellularly activated complement contributes to podocyte and glomerular damage independently of
the deposited circulating complement. Our studies will point to the pursuit of avenues to limit increased
production and activation of complement in podocytes in patients with lupus nephritis.

## Key facts

- **NIH application ID:** 10214745
- **Project number:** 1R21AI151367-01A1
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Abhigyan Satyam
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,750
- **Award type:** 1
- **Project period:** 2021-02-06 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214745

## Citation

> US National Institutes of Health, RePORTER application 10214745, Intracellular complement activation in Lupus Nephritis Podocytes (1R21AI151367-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214745. Licensed CC0.

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