Polydom Is an Extracellular Matrix Protein Involved in Lymphatic Vessel Remodeling

Circ Res. 2017 Apr 14;120(8):1276-1288. doi: 10.1161/CIRCRESAHA.116.308825. Epub 2017 Feb 8.


Rationale: Lymphatic vasculature constitutes a second vascular system essential for immune surveillance and tissue fluid homeostasis. Maturation of the hierarchical vascular structure, with a highly branched network of capillaries and ducts, is crucial for its function. Environmental cues mediate the remodeling process, but the mechanism that underlies this process is largely unknown.

Objective: Polydom (also called Svep1) is an extracellular matrix protein identified as a high-affinity ligand for integrin α9β1. However, its physiological function is unclear. Here, we investigated the role of Polydom in lymphatic development.

Methods and results: We generated Polydom-deficient mice. Polydom-/- mice showed severe edema and died immediately after birth because of respiratory failure. We found that although a primitive lymphatic plexus was formed, it failed to undergo remodeling in Polydom-/- embryos, including sprouting of new capillaries and formation of collecting lymphatic vessels. Impaired lymphatic development was also observed after knockdown/knockout of polydom in zebrafish. Polydom was deposited around lymphatic vessels, but secreted from surrounding mesenchymal cells. Expression of Foxc2 (forkhead box protein c2), a transcription factor involved in lymphatic remodeling, was decreased in Polydom-/- mice. Polydom bound to the lymphangiogenic factor Ang-2 (angiopoietin-2), which was found to upregulate Foxc2 expression in cultured lymphatic endothelial cells. Expressions of Tie1/Tie2 receptors for angiopoietins were also decreased in Polydom-/- mice.

Conclusions: Polydom affects remodeling of lymphatic vessels in both mouse and zebrafish. Polydom deposited around lymphatic vessels seems to ensure Foxc2 upregulation in lymphatic endothelial cells, possibly via the Ang-2 and Tie1/Tie2 receptor system.

Keywords: Polydom/Svep1; embryonic development; extracellular matrix; lymphatic capillary; vascular remodeling.

Publication types

  • Video-Audio Media

MeSH terms

  • Angiopoietin-2 / metabolism
  • Animals
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • Cell Communication
  • Cells, Cultured
  • Edema / genetics
  • Edema / metabolism
  • Edema / physiopathology
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Endothelium, Lymphatic / abnormalities
  • Endothelium, Lymphatic / metabolism
  • Endothelium, Lymphatic / physiopathology
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Genotype
  • Humans
  • Lymphangiogenesis*
  • Lymphatic Vessels / abnormalities
  • Lymphatic Vessels / metabolism*
  • Lymphatic Vessels / physiopathology
  • Mesoderm / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptor, TIE-1 / genetics
  • Receptor, TIE-1 / metabolism
  • Receptor, TIE-2 / genetics
  • Receptor, TIE-2 / metabolism
  • Signal Transduction
  • Thoracic Duct / abnormalities
  • Thoracic Duct / metabolism
  • Thoracic Duct / physiopathology
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism


  • Angiopoietin-2
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • Forkhead Transcription Factors
  • Polydom protein, mouse
  • Proteins
  • Svep1 protein, zebrafish
  • Zebrafish Proteins
  • mesenchyme fork head 1 protein
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Tek protein, mouse