# Targeting Inflammation to Improve FGF23-mediated Mineral Metabolism in CKD

> **NIH NIH F31** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $28,444

## Abstract

Project Summary/Abstract: This NRSA proposal, tailored to Mr. Solis, provides high-quality predoctoral
research training and career development centered upon his future goals. The sponsor’s excellent mentoring
record, collaborations with leading bone and kidney biomedical researchers, and the outstanding environment
at the IUSM and Indiana Center for Musculoskeletal Health (ICMH) will contribute to the successful completion
of this project. Additionally, participation in the Preparing Future Faculty and Professionals program for ethics
and grant writing courses, manuscript preparation, departmental seminars and journal clubs, as well as national
meetings will enhance Mr. Solis’s career development towards becoming a well-rounded, independent
investigator. Previous studies from the sponsor’s lab and others have identified gain- and loss of function
mutations in Fibroblast growth factor-23 (FGF23) that resulted in severe metabolic bone diseases, placing
FGF23 as a hormone central to phosphate metabolism. FGF23 is an important factor in common diseases of
altered phosphate handling such as chronic kidney disease-mineral and bone disorder (CKD-MBD), with high
circulating concentrations associated with patient mortality. Although progress has been made in understanding
basic and clinical aspects of phosphate handling in CKD, the regulatory mechanisms governing FGF23-
dependent phosphate homeostasis remain unclear. Importantly, chronic inflammation arises in CKD with tissue
damage and increased production of inflammatory cytokines. It is known that specific cytokines signal through
NF-κB-mediated mechanisms, however how this pathway influences FGF23 actions is unknown. Indeed, both
renal inflammation and elevated FGF23 are associated with poor outcomes in CKD, therefore identifying
regulatory mechanisms interconnecting FGF23 bioactivity and pro-inflammatory cytokines could provide targets
for therapeutic intervention. Our initial results strongly support novel interactions between these pathways and
FGF23 bioactivity. Thus, my central hypothesis is: NF-κB activity negatively regulates kidney FGF23-mediated
mineral metabolism, and TNFα driven inflammatory responses exacerbate this effect in CKD. In Aim 1, the
mechanisms dictating NF-κB regulation of FGF23 bioactivity will be tested in vitro; and Aim 2 will test TNF
cytokines on FGF23-dependent mineral metabolism in novel models of FGF23 overexpression and in CKD with
genetically ablated TNF signaling. Using these systems, Mr. Solis will gain new research skills in gene targeting
and utilizing state of the art translational mouse models. Collectively, this proposal will provide excellent
research, ethics, and written and oral presentation training to Mr. Solis, as well as test important disease
mechanisms that result in endocrine disturbances of mineral metabolism.

## Key facts

- **NIH application ID:** 10937072
- **Project number:** 5F31DK137439-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Emmanuel Solis
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $28,444
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-04-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937072

## Citation

> US National Institutes of Health, RePORTER application 10937072, Targeting Inflammation to Improve FGF23-mediated Mineral Metabolism in CKD (5F31DK137439-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10937072. Licensed CC0.

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