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Matrix metalloproteinase-19 expression in dermal wounds and by fibroblasts in culture

Niina Hieta1, Ulla Impola, Carlos López-Otín

  • 1Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.

The Journal of Investigative Dermatology
|January 8, 2004
PubMed

Insights

Matrix metalloproteinase-19 (MMP-19) is expressed in human skin wounds and its production by fibroblasts is enhanced by tumor necrosis factor-alpha (TNF-alpha). Signaling pathways including ERK1/2, JNK, and p38 coordinate MMP-19 expression, suggesting a role in wound repair.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Wound Healing Research

Background:

  • Matrix metalloproteinases (MMPs) play crucial roles in tissue remodeling.
  • Matrix metalloproteinase-19 (MMP-19) function in human cutaneous wound healing is not well understood.
  • Understanding MMP-19 regulation is key to developing therapeutic strategies for wound repair.

Purpose of the Study:

  • To investigate the expression of MMP-19 in human cutaneous wounds.
  • To elucidate the regulatory mechanisms of MMP-19 expression in human skin fibroblasts.
  • To identify the signaling pathways involved in MMP-19 induction.

Main Methods:

  • Immunohistochemistry was used to detect MMP-19 expression in wound tissues.
  • Human skin fibroblasts were cultured to study MMP-19 expression.
  • Tumor necrosis factor-alpha (TNF-alpha) was used to induce MMP-19 expression.
  • Specific inhibitors (PD98059, SB203580) and adenoviral vectors were employed to study signaling pathways (ERK1/2, p38, JNK).

Main Results:

  • MMP-19 was detected in fibroblasts, endothelial cells, and macrophages in various human cutaneous wounds.
  • TNF-alpha significantly enhanced MMP-19 mRNA and protein production in cultured fibroblasts.
  • Induction of MMP-19 by TNF-alpha was partially mediated by the ERK1/2 and p38 signaling pathways.
  • Activation of ERK1/2, p38, and JNK pathways individually or in combination led to increased MMP-19 expression.

Conclusions:

  • MMP-19 is expressed in human skin wounds and plays a role in cutaneous repair.
  • TNF-alpha is a potent inducer of MMP-19 expression in dermal fibroblasts.
  • The ERK1/2, JNK, and p38 signaling pathways coordinately regulate MMP-19 expression, influencing fibroblast proteolytic activity.

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