CXCR7 Inhibits Fibrosis via Wnt/ β-Catenin Pathways during the Process of Angiogenesis in Human Umbilical Vein Endothelial Cells

Biomed Res Int. 2020 Jun 5:2020:1216926. doi: 10.1155/2020/1216926. eCollection 2020.

Abstract

Although SDF-1/CXCR7 plays an important role in angiogenesis, the function and the pathway of the SDF-1/CXCR7 axis might depend on the cell type or tissue origin and not fully understood. In this study, we investigated the effect of CXCR7 in SDF-1-induced proliferation, migration, apoptosis, tube formation, and endothelial-to-mesenchymal transition (EndMT) of human umbilical vein endothelial cells (HUVECs), and the potential pathway of SDF-1/CXCR7. We confirmed that the silencing of CXCR7 inhibited the proliferation of HUVECs and contributed the apoptosis, while overexpressed CXCR7 increased SDF-1-induced HUVECs migration and tube formation. However, upregulated CXCR7 inhibited the expression of α-SMA, suggesting that CXCR7 might attenuate EndMT. In addition, overexpressed CXCR7 activated AKT and ERK signaling pathways but suppressed Wnt/β-catenin pathways in HUVECs. The inhibition of Wnt/β-catenin pathways decreased the expression of α-SMA. Altogether, these results suggest that CXCR7 might inhibit fibrosis via Wnt/β-catenin pathways during the process of angiogenesis.

MeSH terms

  • Cell Movement / genetics
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism
  • Fibrosis / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Neovascularization, Physiologic / physiology*
  • Receptors, CXCR* / genetics
  • Receptors, CXCR* / metabolism
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / metabolism*

Substances

  • ACKR3 protein, human
  • CTNNB1 protein, human
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR
  • Wnt Proteins
  • beta Catenin