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Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
Published on: September 30, 2019
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Fibroblast growth factor receptor as a potential candidate for phosphate sensing
Yuichi Takashi1, Seiji Fukumoto2
1Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, Fukuoka.
Current Opinion in Nephrology and Hypertension
|May 20, 2020
Summary
High phosphate levels activate FGFR1c in bone, initiating a signaling pathway that regulates FGF23 production. This discovery reveals a key mechanism for sensing and managing serum phosphate levels.
Area of Science:
- Endocrinology
- Molecular Biology
- Bone Metabolism
Background:
- Phosphate is vital for biological processes, and its levels must be tightly regulated.
- Imbalances like hypophosphatemia and hyperphosphatemia lead to severe health issues such as rickets/osteomalacia and ectopic calcification.
- Fibroblast Growth Factor (FGF) 23 is the primary hormone controlling serum phosphate, produced in bone and acting on kidneys.
Purpose of the Study:
- To elucidate the mechanism by which bone senses serum phosphate levels.
- To understand how bone regulates the production of FGF23 in response to phosphate.
- To identify the molecular players involved in phosphate homeostasis.
Main Methods:
- Investigated the role of Fibroblast Growth Factor Receptor (FGFR) 1c in phosphate sensing.
- Analyzed the downstream signaling pathway activated by extracellular phosphate.
- Examined the regulation of GALNT3 gene expression and its impact on FGF23.
Main Results:
- High extracellular phosphate activates FGFR1c in bone cells.
- Activation of FGFR1c triggers an intracellular signaling cascade.
- This cascade regulates GALNT3 expression, which is crucial for posttranslational modification of FGF23.
Conclusions:
- FGFR1c functions as a critical phosphate-sensing molecule in bone.
- The FGFR1c-GALNT3 axis represents a key regulatory mechanism for FGF23 production.
- These findings reveal a novel feedback system for serum phosphate regulation and the molecular basis of phosphate sensing.
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