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Mast Cell Protease 7 Promotes Angiogenesis by Degradation of Integrin Subunits

Devandir A de Souza Junior1, Carolina Santana2, Gabriel V Vieira3

  • 1Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14.049-900, Brazil. dasjunior@hotmail.com.

Cells
|April 25, 2019
PubMed

Insights

Recombinant mouse mast cell protease-7 (rmMCP-7) directly degrades integrin subunits, initiating angiogenesis. This protease is sufficient to drive new blood vessel formation by impacting endothelial cell migration and tube formation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • Previous studies showed recombinant mouse mast cell protease-7 (rmMCP-7) stimulates endothelial cell spreading and matrix penetration in vitro.
  • Angiogenesis, the formation of new blood vessels, is crucial for development and disease.

Purpose of the Study:

  • To assess the in vivo angiogenesis potential of rmMCP-7.
  • To investigate the relationship between rmMCP-7 and integrins during angiogenesis.

Main Methods:

  • Directed in vivo angiogenesis assay (DIVAA™) to evaluate rmMCP-7's angiogenic capacity.
  • In vitro studies using SVEC4-10 endothelial cells to analyze integrin subunit levels after rmMCP-7 incubation.
  • Experiments with proteasome inhibitors to differentiate degradation pathways.

Main Results:

  • rmMCP-7 induced significant vessel invasion in the DIVAA™ model, unlike controls.
  • rmMCP-7 reduced integrin subunits αv and β1 levels on endothelial cells.
  • Integrin degradation by rmMCP-7 was observed directly and via the ubiquitin/proteasome system.
  • rmMCP-7 promoted endothelial cell migration, tube formation, and loop formation, even with proteasome inhibition.

Conclusions:

  • rmMCP-7 directly degrades integrin subunits, which is sufficient to initiate angiogenesis.
  • This study demonstrates for the first time that mMCP-7 mediates angiogenesis through integrin degradation.
Keywords:
DIVAA™angiogenesisintegrinmast cellproteasesubiquitin/proteasome

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