Dermatopontin regulates fibrin formation and its biological activity

J Invest Dermatol. 2014 Jan;134(1):256-263. doi: 10.1038/jid.2013.305. Epub 2013 Jul 22.

Abstract

Dermatopontin (DP) is a small extracellular matrix component in the dermis. Fibrin is a major component of a provisional matrix that is formed just after wounding. Previously, we found that DP was present in the provisional matrix, and it interacted with fibrin. Here, we examined the role of DP on fibrin function. DP interacted with both the fibrin monomer and fibrils, and was incorporated into the fibrils during fibrin formation. A DP sequence, PHGQVVVAVRS, was identified as a fibrin-binding site, and a globular D domain of fibrin was the binding site for DP. DP accelerated fibrin fibril formation into structurally modified fibrils. Fibrin fibrils formed in the presence of DP enhanced both endothelial cell attachment and cell spreading. The attached cells developed a more organized cytoskeleton when compared with those that attached to fibrin fibrils only. The main receptor for cell adhesion was identified as αvβ3 integrin, and a cooperating receptor was a β1-containing integrin species, probably α5β1 integrin. These results indicate that DP can modify certain biological functions of fibrin, and thus a another function of this extracellular matrix protein was revealed. In addition, the fibrin-DP complex might become useful for developing an improved artificial matrix for improving wound healing.

MeSH terms

  • Binding Sites / physiology
  • Cell Adhesion / physiology
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Cytoskeleton / metabolism
  • Dermis / physiology*
  • Extracellular Matrix Proteins / metabolism*
  • Fibrin / metabolism*
  • Fibrinogen / metabolism
  • Granulation Tissue / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Protein Binding / physiology
  • Wound Healing / physiology*

Substances

  • Chondroitin Sulfate Proteoglycans
  • DPT protein, human
  • Extracellular Matrix Proteins
  • Integrin alphaVbeta3
  • Fibrin
  • Fibrinogen