Collagen of chronically inflamed skin is over-modified and upregulates secretion of matrix metalloproteinase 2 and matrix-degrading enzymes by endothelial cells and fibroblasts

J Invest Dermatol. 2003 Dec;121(6):1317-25. doi: 10.1111/j.1523-1747.2003.12637.x.


In order to investigate the properties of collagen in chronically inflamed tissue, we isolated collagen from the ear skin of mice with chronic contact dermatitis and examined its biochemical characteristics and the functions that regulate the secretion of matrix metalloproteinase 2 and collagen-degrading enzymes from endothelial cells and fibroblasts. Collagen in skin with chronic contact dermatitis comprised 60% type I collagen and 40% type III collagen, which latter is higher than the content of type III collagen in control skin (35%). The denaturation temperature was higher (42 degrees C) than that of control skin (39 degrees C). The alpha2 chain of type I collagen was over-hydroxylated at both proline and lysine residues. Segment-long-spacing crystallites of type I collagen were unusually connected in tandem. Collagen of chronically inflamed skin was less susceptible to matrix metalloproteinase 2 after heat denaturation. Endothelial cells and fibroblasts secreted an increased amount of matrix metalloproteinase 2 when cultured on a gel formed from the collagen of chronically inflamed skin. Collagen-degrading activity secreted from fibroblasts was also upregulated when cells were in contact with collagen of chronically inflamed skin. These results suggest that the collagen in chronically inflamed tissue has altered biochemical characteristics and functions, which may affect the pathogenesis of the chronic skin disease.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chronic Disease
  • Collagen Type I / chemistry
  • Collagen Type I / metabolism*
  • Collagen Type I / ultrastructure
  • Collagen Type III / chemistry
  • Collagen Type III / metabolism*
  • Collagen Type III / ultrastructure
  • Crystallization
  • Dermatitis, Contact / metabolism*
  • Endothelial Cells / cytology
  • Endothelial Cells / enzymology
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • In Vitro Techniques
  • Matrix Metalloproteinase 2 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron
  • Skin / metabolism*
  • Up-Regulation


  • Collagen Type I
  • Collagen Type III
  • Matrix Metalloproteinase 2