Wnt-7a up-regulates matrix metalloproteinase-12 expression and promotes cell proliferation in corneal epithelial cells during wound healing.
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.
Lyu
Jungmook
J
Department of Ophthalmology and Visual Science, College of Medicine, Catholic University of Korea, Seoul 137-040, Korea.
Joo
Choun-Ki
CK
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D003315:Cornea / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D051153:Wnt Proteins; D014945:Wound Healing; D051176:beta Catenin; D020744:rac GTP-Binding Proteins / Q000378:metabolism
C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C092778:WNT7A protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D008156:Luciferases; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; D020744:rac GTP-Binding Proteins