September 1996
Volume 37, Issue 10
Free
Articles  |   September 1996
Platelet-activating factor enhances urokinase-type plasminogen activator gene expression in corneal epithelium.
Author Affiliations
  • Y Tao
    LSU Eye Center, School of Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
  • H E Bazan
    LSU Eye Center, School of Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
  • N G Bazan
    LSU Eye Center, School of Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
Investigative Ophthalmology & Visual Science September 1996, Vol.37, 2037-2046. doi:
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Y Tao, H E Bazan, N G Bazan; Platelet-activating factor enhances urokinase-type plasminogen activator gene expression in corneal epithelium.. Invest. Ophthalmol. Vis. Sci. 1996;37(10):2037-2046.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

PURPOSE: To determine whether platelet-activating factor (PAF), a lipid mediator that is accumulated in the cornea after alkali burn, induces the gene expression of urokinase-type plasminogen activator (uPA) in the corneal epithelium. Possible signaling mechanisms of uPA gene induction by PAF also were examined. METHODS: Rabbit corneas were cultured with or without PAF. One hour before stimulation, PAF antagonists or other modulators were added to PAF. In some experiments, the corneas were permeabilized to introduce guanosine triphosphate analogs into the corneal epithelial cells. Corneal epithelia were then harvested for Northern blot analysis, nuclear runoff transcription assay, and zymography. RESULTS: Platelet-activating factor induced uPA mRNA expression in the corneal epithelium. New protein synthesis was not required for the induction of uPA mRNA. The induction was at the level of transcription as shown by nuclear runoff assays. Additionally, both actinomycin D and alpha-amanitin inhibited the increase in uPA mRNA by PAF. The message was translated into protein, which was secreted into the conditioned medium. An antagonist with high affinity for intracellular PAF binding sites (BN 50730) inhibited uPA gene expression and cellular secretion of the protein. The effect of PAF was not mediated by G proteins and was independent of protein kinase C- and cyclic adenosine monophosphate-dependent signal transduction pathways. Okadaic acid increased the expression of uPA and, at longer times, augmented the effect of PAF, suggesting that a signaling pathway that requires phosphorylation is involved in activated uPA mRNA synthesis. CONCLUSIONS: After corneal injury and inflammation, PAF may be an important initiator of the proteolytic cascade, leading to epithelial defects and corneal ulceration. Antagonists of PAF could be useful in the prevention of these diseases.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×