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Updated: Jan 30, 2026

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
Published on: September 30, 2019
Small Peptide Modulation of Fibroblast Growth Factor Receptor 3-Dependent Postnatal Lymphangiogenesis
David P Perrault1, Gene K Lee1, Sun Young Park1
11 Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
Background:
The fibroblast growth factor receptor (FGFR) family includes transmembrane receptors involved in a wide range of developmental and postdevelopmental biologic processes as well as a wide range of human diseases. In particular, FGFR3 has been implicated in the mechanism by which 9-cis retinoic acid (9-cisRA) induces lymphangiogenesis and improves lymphedema. The purpose of this study was to validate the efficacy of a novel small peptide FGFR3 inhibitor, peptide P3 (VSPPLTLGQLLS), and to elucidate the role of FGFR3 in 9-cisRA-induced lymphangiogenesis using this peptide.
Methods And Results:
Peptide P3 effectively inhibited FGFR3 phosphorylation. In vitro, peptide P3-mediated FGFR3 inhibition did not decrease lymphatic endothelial cell (LEC) proliferation, migration, or tubule formation. However, peptide P3-mediated FGFR3 inhibition did block 9-cisRA-stimulated LEC proliferation, migration, and tubule formation. In vivo, peptide P3-mediated FGFR3 inhibition was sufficient to inhibit 9-cisRA-induced tracheal lymphangiogenesis.
Conclusion:
FGFR3 does not appear to be essential to nonpromoted LEC proliferation, migration, and tubule formation. However, FGFR3 may play a key role in LEC proliferation, migration, tubule formation, and postnatal in vivo lymphangiogenesis when pharmacologically induced by 9-cisRA. P3 may have the potential to be used as a precise regulatory control element for 9-cisRA-mediated lymphangiogenesis.
Insights
Fibroblast growth factor receptor 3 (FGFR3) inhibition blocks 9-cis retinoic acid-induced lymphangiogenesis without affecting normal lymphatic endothelial cell function. This suggests FGFR3 plays a key role in promoting lymphatic vessel growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Developmental Biology
Background:
- Fibroblast growth factor receptor (FGFR) family are transmembrane receptors crucial for development, cell function, and disease.
- FGFR3 is implicated in 9-cis retinoic acid (9-cisRA)-induced lymphangiogenesis and lymphedema improvement.
Purpose of the Study:
- To validate the efficacy of a novel small peptide FGFR3 inhibitor, peptide P3.
- To elucidate FGFR3's role in 9-cisRA-induced lymphangiogenesis using peptide P3.
Main Methods:
- In vitro studies assessed peptide P3's effect on lymphatic endothelial cell (LEC) proliferation, migration, and tubule formation.
- In vivo studies evaluated peptide P3's impact on 9-cisRA-induced tracheal lymphangiogenesis.
Main Results:
- Peptide P3 effectively inhibited FGFR3 phosphorylation.
- FGFR3 inhibition by peptide P3 did not impede normal LEC proliferation, migration, or tubule formation.
- Peptide P3-mediated FGFR3 inhibition blocked 9-cisRA-stimulated LEC proliferation, migration, tubule formation, and in vivo lymphangiogenesis.
Conclusions:
- FGFR3 is not essential for basal LEC functions but plays a key role in 9-cisRA-induced lymphangiogenesis.
- Peptide P3 demonstrates potential as a specific regulator of 9-cisRA-mediated lymphatic vessel growth.
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