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Involvement of PAR-2 in the Induction of Cell-Specific Matrix Metalloproteinase-2 by Activated Protein C in Cutaneous Wound Healing

International Journal of Molecular Sciences, ISSN: 1422-0067, Vol: 25, Issue: 1
2024
  • 4
    Citations
  • 0
    Usage
  • 4
    Captures
  • 2
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

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  • Citations
    4
  • Captures
    4
  • Mentions
    2
    • Blog Mentions
      1
      • Blog
        1
    • News Mentions
      1
      • News
        1

Most Recent News

Reports Summarize Blood Proteins Research from University of Sydney (Involvement of PAR-2 in the Induction of Cell-Specific Matrix Metalloproteinase-2 by Activated Protein C in Cutaneous Wound Healing)

2024 JAN 12 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Life Science Daily -- New study results on blood proteins have been

Article Description

We previously reported that human keratinocytes express protease-activated receptor (PAR)-2 and play an important role in activated protein C (APC)-induced cutaneous wound healing. This study investigated the involvement of PAR-2 in the production of gelatinolytic matrix metalloproteinases (MMP)-2 and -9 by APC during cutaneous wound healing. Full-thickness excisional wounds were made on the dorsum of male C57BL/6 mice. Wounds were treated with APC on days 1, 2, and 3 post-wounding. Cultured neonatal foreskin keratinocytes were treated with APC with or without intact PAR-2 signalling to examine the effects on MMP-2 and MMP-9 production. Murine dermal fibroblasts from PAR-2 knock-out (KO) mice were also assessed. MMP-2 and -9 were measured via gelatin zymography, fluorometric assay, and immunohistochemistry. APC accelerated wound healing in WT mice, but had a negligible effect in PAR-2 KO mice. APC-stimulated murine cutaneous wound healing was associated with the differential and temporal production of MMP-2 and MMP-9, with the latter peaking on day 1 and the former on day 6. Inhibition of PAR-2 in human keratinocytes reduced APC-induced MMP-2 activity by 25~50%, but had little effect on MMP-9. Similarly, APC-induced MMP-2 activation was reduced by 40% in cultured dermal fibroblasts derived from PAR-2 KO mice. This study shows for the first time that PAR-2 is essential for APC-induced MMP-2 production. Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR-2.

Bibliographic Details

Julovi, Sohel M; McKelvey, Kelly; Minhas, Nikita; Chan, Yee-Ka Agnes; Xue, Meilang; Jackson, Christopher J

MDPI AG

Chemical Engineering; Biochemistry, Genetics and Molecular Biology; Chemistry; Computer Science

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