Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis

Biochem Biophys Res Commun. 2010 Jan 22;391(4):1762-8. doi: 10.1016/j.bbrc.2009.12.150. Epub 2009 Dec 31.


Chemerin acting via its distinct G protein-coupled receptor CMKLR1 (ChemR23), is a novel adipokine, circulating levels of which are raised in inflammatory states. Chemerin shows strong correlation with various facets of the metabolic syndrome; these states are associated with an increased incidence of cardiovascular disease (CVD) and dysregulated angiogenesis. We therefore, investigated the regulation of ChemR23 by pro-inflammatory cytokines and assessed the angiogenic potential of chemerin in human endothelial cells (EC). We have demonstrated the novel presence of ChemR23 in human ECs and its significant up-regulation (P<0.001) by pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. More importantly, chemerin was potently angiogenic, as assessed by conducting functional in-vitro angiogenic assays; chemerin also dose-dependently induced gelatinolytic (MMP-2 & MMP-9) activity of ECs (P<0.001). Furthermore, chemerin dose-dependently activated PI3K/Akt and MAPKs pathways (P<0.01), key angiogenic and cell survival cascades. Our data provide the first evidence of chemerin-induced endothelial angiogenesis and MMP production and activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capillaries / growth & development
  • Cell Proliferation
  • Chemokines / metabolism
  • Chemokines / pharmacology
  • Cytokines / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neovascularization, Physiologic*
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • CMKLR1 protein, human
  • Chemokines
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • RARRES2 protein, human
  • Receptors, Chemokine
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9