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
  • 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.
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