2. Academic Validation
  3. Small Peptide Modulation of Fibroblast Growth Factor Receptor 3-Dependent Postnatal Lymphangiogenesis

Small Peptide Modulation of Fibroblast Growth Factor Receptor 3-Dependent Postnatal Lymphangiogenesis

  • Lymphat Res Biol. 2019 Feb;17(1):19-29. doi: 10.1089/lrb.2018.0035.
David P Perrault 1,  Gene K Lee 1,  Sun Young Park 1,  Sunju Lee 2,  Dongwon Choi 2,  Eunson Jung 2,  Young Jin Seong 2,  Eun Kyung Park 2,  Cynthia Sung 1,  Roy Yu 1,  Antoun Bouz 1,  Austin Pourmoussa 1,  Soo Jung Kim 1,  Young-Kwon Hong 2,  Alex K Wong 1
Affiliations

Affiliations

  • 1 1 Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • 2 2 Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
PMID: 30648916 DOI: 10.1089/lrb.2018.0035
Abstract

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.

Keywords

9-cis retinoic acid; FGFR3; VSPPLTLGQLLS; lymphangiogenesis; lymphatic endothelial cell; lymphedema; peptide inhibitor.

Figures
Products