4-Methylumbelliferone induces the expression of membrane type 1-matrix metalloproteinase in cultured human skin fibroblasts

Biochem Biophys Res Commun. 2002 Nov 15;298(5):646-50. doi: 10.1016/s0006-291x(02)02516-0.


Human skin fibroblasts were cultured in the presence of 4-methylumbelliferone, an inhibitor of hyaluronan synthesis. Gelatinolytic activity excreted in the medium was examined by zymography and gelatinase assay using a fluorogenic substrate. 4-Methylumbelliferone added to the medium activated the latent form of matrix metalloproteinase-2 in a dose- and time-dependent manner. Immunoblot analysis also showed the conversion of the latent form of matrix metalloproteinase-2 to its active form. This activation was observed even when the cells were cultured with both 4-methylumbelliferone and hyaluronan. Addition of Streptomyces hyaluronidase to the medium during cultivation did not activate the latent form of matrix metalloproteinase-2. Reverse transcription-polymerase chain reaction revealed that 4-methylumbelliferone markedly increased the level of mRNA for membrane type 1-matrix metalloproteinase, whereas levels of mRNA for matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 were little affected. These results suggest that 4-methylumbelliferone induces the expression of membrane type 1-matrix metalloproteinase, resulting in activation of matrix metalloproteinase-2, in cultured human skin fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Enzyme Induction / drug effects
  • Enzyme Precursors / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gelatinases / metabolism
  • Gene Expression / drug effects
  • Humans
  • Hyaluronic Acid / pharmacology
  • Hymecromone / pharmacology*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / drug effects
  • Skin / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism


  • Enzyme Precursors
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-2
  • Hymecromone
  • Hyaluronic Acid
  • Gelatinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • progelatinase
  • Matrix Metalloproteinase 2