Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor

Michelle E. LeBlanc, Weiwen Wang, Nora B. Caberoy, Xiuping Chen, Feiye Guo, Gabriela Alvarado, Chen Shen, Feng Wang, Hui Wang, Rui Chen, Zhao-Jun Liu, Keith A Webster, Wei Li

Research output: Contribution to journalArticle

11 Scopus citations


Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functional roles and molecular signaling. We combined open reading frame phage display with multi-round in vivo binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its in vitro angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase 1/2(ERK1/2) pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor.

Original languageEnglish (US)
Article numbere0127904
JournalPLoS One
Issue number5
StatePublished - May 21 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    LeBlanc, M. E., Wang, W., Caberoy, N. B., Chen, X., Guo, F., Alvarado, G., Shen, C., Wang, F., Wang, H., Chen, R., Liu, Z-J., Webster, K. A., & Li, W. (2015). Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor. PLoS One, 10(5), [e0127904]. https://doi.org/10.1371/journal.pone.0127904