The expression of glia maturation factors and the effect of glia maturation factor-γ on angiogenic sprouting in zebrafish

Exp Cell Res. 2013 Mar 10;319(5):707-17. doi: 10.1016/j.yexcr.2013.01.004. Epub 2013 Jan 16.

Abstract

Angiogenesis is a vital process for proper embryonic development, wound healing, malignant tumor growth and metastasis. Two glia maturation factor genes, glia maturation factor-β (GMFB) and glia maturation factor-γ (GMFG), presenting different expression patterns and distinct biological functions are found in vertebrates. But, the role of GMFB and GMFG in vascular development remains largely unknown. Here, we showed that both GMFB and GMFG are highly conserved in vertebrates. Whole-mount in situ hybridization and quantitative RT-PCR results revealed that GMFB and GMFG were differently expressed during zebrafish embryogenesis. GMFB was highly enriched in brain and GMFG was predominantly expressed in endothelial cells. By gene specific MO, knockdown of GMFG, but not GMFB, severely disrupted angiogenic sprouting of intersegmental vessels (ISVs), but this angiogenic defects were prevented by overexpression of a MO-resistant form of zebrafish GMFG mRNA. In addition, the expressions of angiogenic factors VEGF-A, STAT3, MMP2, MMP9, and MMP13 were significantly decreased in endothelial cells of GMFG morphants. Our findings provide the first in vivo evidence that GMFG is an important regulator for angiogenic sprouting during angiogenesis in zebrafish and suggest that GMFG may act as a novel potential target for anti-angiogenesis therapy in clinical settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Gene Expression Regulation, Developmental*
  • Glia Maturation Factor / antagonists & inhibitors
  • Glia Maturation Factor / genetics
  • Glia Maturation Factor / metabolism*
  • In Situ Hybridization
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neovascularization, Physiologic*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Zebrafish / embryology
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Glia Maturation Factor
  • RNA, Messenger
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Vascular Endothelial Growth Factor A
  • Zebrafish Proteins
  • glia maturation factor gamma
  • stat3 protein, zebrafish
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9