Wnt-7a up-regulates matrix metalloproteinase-12 expression and promotes cell proliferation in corneal epithelial cells during wound healing

J Biol Chem. 2005 Jun 3;280(22):21653-60. doi: 10.1074/jbc.M500374200. Epub 2005 Mar 31.


Corneal wound repair involves the rapid coverage of a denuded area by residual epithelial cells. During wound healing, there are different cell behaviors in different regions of the epithelium: cell proliferation in the peripheral epithelium and cell migration in the central epithelium. We found that Wnt-7a was rapidly induced in the wounded cornea, promoted the proliferation of corneal epithelial cells, and enhanced wound closure. Matrix metalloproteinase-12 (MMP-12) was detected in the peripheral epithelium, where cell proliferation was enhanced, but was diminished in the migrating central epithelium. Wnt-7a induced the accumulation of beta-catenin and the activation of Rac and beta-catenin, and Rac synergistically induced the transcription of MMP-12. Blocking the function of MMP-12 delayed wound closure induced by Wnt-7a. Our results also suggest that, in addition to the beta-catenin pathway, Wnt-7a might induce a beta-catenin-independent pathway. By regulating the proliferation of corneal epithelial cells, Wnt-7a and MMP-12 appear to contribute to corneal wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Blotting, Western
  • Cell Culture Techniques
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Cornea / cytology
  • Cornea / metabolism
  • Cytoskeletal Proteins / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / enzymology*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Luciferases / metabolism
  • Matrix Metalloproteinase 12
  • Metalloendopeptidases / biosynthesis*
  • Organ Culture Techniques
  • Plasmids / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / metabolism
  • Transcriptional Activation
  • Up-Regulation*
  • Wnt Proteins
  • Wound Healing
  • beta Catenin
  • rac GTP-Binding Proteins / metabolism


  • CTNNB1 protein, human
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • WNT7A protein, human
  • Wnt Proteins
  • beta Catenin
  • Luciferases
  • Metalloendopeptidases
  • MMP12 protein, human
  • Matrix Metalloproteinase 12
  • rac GTP-Binding Proteins