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Regulation of MMP-2 gene transcription in dermal wounds

Petra Lynen Jansen1, Raphael Rosch, Marc Jansen

  • 1Interdisciplinary Centre for Clinical Research BIOMAT, University Hospital, RWTH Aachen, Aachen, Germany. plynen@ukaachen.de

The Journal of Investigative Dermatology
|March 9, 2007
PubMed

Insights

Skin injury upregulates matrix metalloproteinase-2 (MMP-2) transcription. A key enhancer element, RE-1, is crucial for this injury-induced MMP-2 gene activation in the skin.

Area of Science:

  • Molecular Biology
  • Dermatology
  • Wound Healing Research

Background:

  • Matrix metalloproteinase-2 (MMP-2) is vital for angiogenesis, inflammation, and fibrosis, processes integral to skin wound healing.
  • Elevated MMP-2 expression is observed following skin injury, indicating its role in the repair process.

Purpose of the Study:

  • To investigate the transcriptional activation mechanisms of the MMP-2 gene in response to skin injury.
  • To identify specific regulatory elements responsible for MMP-2 gene induction after skin damage.

Main Methods:

  • Utilized two distinct MMP-2/LacZ-reporter mouse models to track MMP-2 gene expression.
  • Analyzed reporter gene expression and MMP-2 proteolytic activity in injured versus normal skin tissues.
  • Performed deletion analysis of MMP-2 regulatory sequences to pinpoint critical functional elements.

Main Results:

  • Skin injury significantly upregulated MMP-2 expression and proteolytic activity, with reporter gene expression primarily in endothelial cells and macrophages.
  • The MMP-2 regulatory sequences from -1686/+423 were sufficient to drive injury-induced promoter activation.
  • Deletion of the RE-1 element (at -1241/+423 bp) abrogated MMP-2 transcription in vivo, highlighting its essential role.

Conclusions:

  • The enhancer element RE-1 is a critical determinant of MMP-2 transcription following skin injury.
  • Understanding MMP-2 regulation by RE-1 provides insights into molecular mechanisms of skin repair and potential therapeutic targets.

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