DDR2 plays a role in fibroblast migration independent of adhesion ligand and collagen activated DDR2 tyrosine kinase

Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):39-44. doi: 10.1016/j.bbrc.2012.10.103. Epub 2012 Nov 3.

Abstract

Discoidin domain receptor-2 (DDR2) is a cell surface tyrosine kinase receptor that can be activated by soluble collagen and has been implicated in diverse physiological functions including organism growth and wound repair. In the current studies, we used fibronectin and collagen-coated 2D surfaces and collagen matrices in combination with siRNA technology to investigate the role of DDR2 in a range of fibroblast motile activities. Silencing DDR2 with siRNA inhibited cell spreading and migration, and similar inhibition occurred regardless whether cells were interacting with fibronectin or collagen surfaces. Under the assay conditions used, DDR2 tyrosine kinase activation was not observed unless soluble collagen was added to the incubation medium. Finally silencing DDR2 also inhibited human fibroblast migration in 3D collagen matrices but had no effect on 3D collagen matrix remodeling and contraction. Taken together, our findings suggest that DDR2 is required for normal fibroblast spreading and migration independent of adhesion ligand and collagen activation of DDR2 tyrosine kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Movement*
  • Cells, Cultured
  • Collagen / metabolism*
  • Discoidin Domain Receptors
  • Enzyme Activation
  • Fibroblasts / enzymology
  • Fibroblasts / physiology*
  • Humans
  • Ligands
  • RNA, Small Interfering / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / physiology*
  • Solubility

Substances

  • Ligands
  • RNA, Small Interfering
  • Receptors, Mitogen
  • Collagen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases