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 Webster, Wei Li

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16 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
Externally publishedYes

ASJC Scopus subject areas

  • General


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