The effects of YKL-40 on angiogenic potential of HUVECs are partly mediated by syndecan-4

Int J Med Sci. 2021 Oct 15;18(16):3759-3767. doi: 10.7150/ijms.55406. eCollection 2021.

Abstract

Background: YKL-40, a secreted glycoprotein, has a role in promoting tumor angiogenesis through syndecan-1 receptor. Syndecan-4 is a member of syndecan family. However, the effects of YKL-40 on migration and tube formation of human umbilical vein cells (HUVECs) mediated by syndecan-4 receptor are unknown. Materials and methods: HUVECs were transfected with lentivirus encoding syndecan-4 short hairpin (sh) RNAs (lenti-synd4 shRNAs) and the efficiency of transfection was measured using qRT-PCR and western blotting. The effects of recombinant protein of YKL-40 on migration and angiogenesis of HUVECs adjusted by syndecan-4 were determined by wound healing and tube formation assay. The expressions of protein kinase Cα (PKCα) and extracellular signal regulated kinases (ERKs) 1 and 2 (ERK1/2) in HUVECs were measured using western blotting. Results: The mRNA and protein expression of syndecan-4 were significantly decreased in HUVECs successfully transfected with lenti-synd4 shRNAs. Lenti-synd4 shRNAs remarkably inhibited the migration and tube formation of HUVECs stimulated by recombinant protein of YKL-40. The levels of PKCα and ratio of p-ERK1/2 to ERK1/2 in HUVECs were also decreased by down-regulating syndecan-4. Conclusion: The effects of YKL-40 on migration and tube formation of HUVECs are partly inhibited by knock-downing syndecan-4 through suppressing PKCα and ERK1/2 signaling pathways.

Keywords: Migration; Signaling pathways; Syndecan-4; Tube formation; YKL-40.

MeSH terms

  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Chitinase-3-Like Protein 1 / antagonists & inhibitors
  • Chitinase-3-Like Protein 1 / physiology*
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / physiology*
  • Humans
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics*
  • RNA, Small Interfering / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Syndecan-4 / antagonists & inhibitors
  • Syndecan-4 / physiology*

Substances

  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • RNA, Small Interfering
  • SDC4 protein, human
  • Syndecan-4