# The role of cytosolic nucleotide sensors in inflammatory fibrosis

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $509,086

## Abstract

It is estimated that fibrosis contributes to 45 percent of all deaths in the developed world. Inflammatory fibrosis
is the histological manifestation of chronic kidney disease (CKD). The critical unresolved question in the field is
the actual trigger and mechanism for the persistent low-grade inflammation in fibrosis. We propose that cytosolic
nucleotide (RNA and DNA) sensing pathways plays key role in inflammatory fibrosis in CKD. Cytosolic DNA and
double stranded, modified RNA is associated with infections is rapidly recognized by cytosolic pattern recognition
receptors (cPRR) including the cytosolic RIG-I-like receptors (RLR), and the cyclic GMP-AMP synthase (cGAS)–
stimulator of interferon genes (STING). Activation of RLR and STING, usually via the TBK1 (TANK-binding)
kinase, NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) and IRF3/7 transcription factors
will trigger the production cytokines, chemokines, activate dendritic cells, and promote T cell expansion, creating
a fibroinflammatory milleu in the kidney.
In this project; We will explore the cause of excessive activation of cytosolic DNA and RNA sensors in
inflammatory fibrosis. Systematically map cytosolic DNA and RNA: A) expression of TEs and ERVs B) cytosolic
mitochondrial DNA in kidneys of patients and mouse models of CKD and fibrosis and their correlation with
cytosolic DNA and RNA sensors. We will define the contribution of myeloid and epithelial, DNA (cGAS/STING)
and RNA (RIG-I, MDA5) sensing pathways to inflammatory fibrosis in mouse models. We will examine whether
genetic variants observed in cytosolic RNA and DNA sensing pathway associated genes (TREX1, TRIM6 and
IRF5) contribute to kidney disease development in patients.

## Key facts

- **NIH application ID:** 10435065
- **Project number:** 1R01DK132630-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** KATALIN SUSZTAK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $509,086
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435065

## Citation

> US National Institutes of Health, RePORTER application 10435065, The role of cytosolic nucleotide sensors in inflammatory fibrosis (1R01DK132630-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10435065. Licensed CC0.

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