# Targeting Aberrant Expression of Cytokines/Chemokines for an Inflammatory Nephritis Cure

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2022 · $236,250

## Abstract

TARGETING ABERRANT EXPRESSION OF CYTOKINES/CHEMOKINES FOR AN INFLAMMATORY
NEPHRITIS CURE
PROJECT SUMMARY / ABSTRACT
Lupus nephritis (LN) is an autoimmune, immune complex-mediated glomerulonephritis (GN), which is a
frequent complication of systemic lupus erythematosus (SLE). Aberrant expression of inflammatory mediators
and tissue injury characterize the early and later stages of LN. There is ongoing unmet need for therapies to
attenuate the effects of early inflammation and the conversion of acute kidney injury to chronic damage in LN.
We previously demonstrated that MG53, most commonly recognized as protein product of skeletal muscles,
can mediate repair of damaged cell membranes, and can modulate cytokine expression in virally-infected
macrophage. Of potential systemic importance, MG53 circulates and transgenic mice with a sustained
elevation of circulating MG53 have a normal lifespan, but show enhanced regenerative capacity following a
tissue injury. Mechanistically, MG53 interacts with tristetraprolin (TTP), a RNA binding protein that mediates
mRNA 3’UTR degradation, an effect that maintains immune homeostasis by regulating the expression of many
inflammatory cytokines and chemokines. We postulated that by manipulating circulating MG53 levels we will
be able to attenuate renal inflammation and prevent tissue damage in LN. This proposal will use mouse
genetics, tissue pathology, biochemical, molecular cellular studies and microscopy imaging to determine
whether circulating MG53 can be sustained chronically to treat LN. Two specific aims are proposed. In Aim1,
we will perform proof-of-concept studies to investigate the anti-inflammatory and tissue-repair effects of
circulating MG53 in well-characterized lupus-prone mice. The feasibility of a novel DNA-modified microvesicle
delivery system to achieve a stable elevation of circulating MG53 will be explored. In Aim 2, we will elucidate
the underlying molecular mechanisms of MG53-mediated control of TTP signaling to modulate the expression
of the inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1), as a model for how MG53 may
be used to control cytokine expression in active LN.

## Key facts

- **NIH application ID:** 10525534
- **Project number:** 1R21AI166273-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Pei-Hui Lin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2022-06-22 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525534

## Citation

> US National Institutes of Health, RePORTER application 10525534, Targeting Aberrant Expression of Cytokines/Chemokines for an Inflammatory Nephritis Cure (1R21AI166273-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10525534. Licensed CC0.

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