Pax-6 expression and activity are induced in the reepithelializing cornea and control activity of the transcriptional promoter for matrix metalloproteinase gelatinase B

Jeremy M. Sivak, Royce Mohan, William B. Rinehart, Pin Xian Xu, Richard L. Maas, M. Elizabeth Fini

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Recent evidence supports the idea that matrix metalloproteinases (MMPs) act as morphogenetic regulators in embryonic and adult events of tissue remodeling. MMP activity is controlled primarily at the level of gene expression. In a regent study we characterized the transcriptional promoter of the MMP gene, gelatinase B (gelB), in transgenic mice, demonstrating the requirement for DNA sequences between -522 and +19 for appropriate activity. In this study we investigated factors required for gelB promoter activity in the developing eye and reepithelializing adult cornea. Pax-6 is a homeobox and paired domain transcription factor that acts at the top of the hierarchy of genes controlling eye development. Pax-6 is also expressed in the adult eye. We show here that the tissue expression pattern of Pax-6 overlaps extensively with gelB promoter activity in the developing and adult eye. In addition Pax-6 is observed to be upregulated in repairing corneal epithelium, as is gelB promoter activity. In cell culture transfection experiments, we identified two promoter regions which mediate positive response to Pax-6. By electrophoretic mobility shift assay, we further pinpoint two Pax-6 binding sites within these response regions and demonstrate direct interaction of the Pax-6 paired domain with one of these sites. These data suggest a mechanism by which Pax-6 may direct gelB expression in an eye-specific manner. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)41-54
Number of pages14
JournalDevelopmental Biology
Volume222
Issue number1
DOIs
StatePublished - 1 Jun 2000
Externally publishedYes

Keywords

  • Cornea
  • Epithelium
  • Eye
  • Gelatinase B
  • MMP-9
  • Matrix metalloproteinase
  • Pax- 6
  • Wound healing

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