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Related Experiment Videos

Vitamin D3 and calcipotriol decrease extracellular plasminogen activator activity in cultured keratinocytes

K Koli1, J Keski-Oja

  • 1Department of Virology, University of Helsinki, Finland.

The Journal of Investigative Dermatology
|November 1, 1993
PubMed
Summary
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Vitamin D3 and calcipotriol reduce plasminogen activator (PA) activity in keratinocytes. These vitamin D compounds decrease urokinase-type PA (u-PA) and tissue-type PA (t-PA) levels, impacting cell growth and differentiation.

Area of Science:

  • Dermatology
  • Cell Biology
  • Biochemistry

Background:

  • Vitamin D3 and its metabolites influence cell growth and differentiation.
  • Calcipotriol, a vitamin D analogue, treats psoriasis, a condition linked to increased plasminogen activator (PA) activity.
  • Keratinocytes play a key role in skin biology and are affected by vitamin D.

Purpose of the Study:

  • To investigate the effects of vitamin D3 and calcipotriol on plasminogen activator (PA) production in human and mouse keratinocytes.
  • To determine the specific types of PA affected and the underlying molecular mechanisms.

Main Methods:

  • Caseinolysis-in-agarose assays to measure total PA activity.
  • Zymographic analyses to identify specific PA types (u-PA, t-PA) and their localization.

Related Experiment Videos

  • Immunoblotting to assess u-PA protein levels.
  • Northern hybridization to analyze urokinase mRNA levels.

    • Main Results:

    • Vitamin D3 and calcipotriol significantly decreased total PA activity in keratinocytes.
    • Urokinase-type plasminogen activator (u-PA) was identified as the primary secreted PA, and its activity, protein, and mRNA levels were reduced.
    • Both calcipotriol and vitamin D3 decreased tissue-type PA (t-PA) activity, mainly associated with extracellular matrices and cell membranes.
    • Calcipotriol reduced u-PA activity even in the presence of known inducers like TGF-β, EGF, and PMA.
    • Paradoxically, calcipotriol treatment led to decreased secretion and deposition of plasminogen activator inhibitor type 1 (PAI-1).

    Conclusions:

    • Vitamin D3 and calcipotriol exert a significant inhibitory effect on plasminogen activator activity in cultured keratinocytes.
    • This reduction in PA activity, particularly u-PA, may contribute to the anti-proliferative and differentiation-inducing effects of vitamin D analogues in keratinocytes.
    • The findings provide insights into the molecular mechanisms underlying the therapeutic efficacy of calcipotriol in conditions like psoriasis.