PMID- 12014920
OWN - NLM
STAT- MEDLINE
DCOM- 20020719
LR  - 20071114
IS  - 0014-4835 (Print)
IS  - 0014-4835 (Linking)
VI  - 74
IP  - 3
DP  - 2002 Mar
TI  - Platelet-activating factor induces the gene expression of TIMP-1, -2, and PAI-1: 
      imbalance between the gene expression of MMP-9 and TIMP-1 and -2.
PG  - 393-402
AB  - Previous studies in the laboratory have shown that platelet-activating factor 
      (PAF), a potent inflammatory mediator that accumulates rapidly in the cornea 
      after an injury, stimulates the expression of urokinase (uPA) and matrix 
      metalloproteinase-1 (MMP-1) and -9 (MMP-9). Tissue inhibitors of MMPs (TIMPs) and 
      plasminogen activator inhibitor (PAI-1) are produced in conjunction with these 
      enzymes and are important regulators of their activity. Here, the authors 
      investigated how PAF affects the expression of PAI-1, TIMP-1 and -2 relative to 
      that of uPA, MMP-1, and -9 in rabbit corneal epithelial cells. Rabbit corneas 
      were incubated in MEM medium containing 100 nM cPAF. To block the effects of PAF 
      in some studies, corneas were preincubated for 1 hr in the presence of the PAF 
      antagonist BN50730 (10 microM). At several time intervals, mRNA was extracted 
      from epithelial cells and the levels of gene expression for the enzymes and their 
      inhibitors were determined by real-time PCR. All quantitations were normalized to 
      the 18s rRNA values (endogenous control) and changes in gene expression were 
      reported as fold increase relative to untreated controls. PAF produced a 20-fold 
      increase in the gene expression of PAI-1 at 8 hr, while similar fold increases in 
      uPA mRNA expression occurred at 2 hr. PAF treatment also stimulated the 
      expression of TIMP-1 and -2 genes, with a six-fold increase in TIMP-1 expression 
      occurring at 36 hr and a four-fold increase in TIMP-2 expression at 24 hr. 
      Maximal induction of MMP-1 and -9 mRNA, on the other hand, occurred at 4 and 8 
      hr, respectively. Induction of MMP-1 gene expression was similar to that of its 
      inhibitors TIMP-1 and -2, while MMP-9 mRNA induction exceeded that of these 
      inhibitors by 100-fold. The PAF-induced expression of PAI-1, TIMP-1 and -2 mRNAs 
      was abolished by pre-treatment with BN50730. These data indicate that PAF 
      activates the gene expression of TIMP-1, -2, and PAI-1 in corneal epithelium by a 
      receptor-mediated mechanism. Furthermore, PAF induced overexpression of MMP-9 
      mRNA relative to that of TIMP-1 and -2, suggesting an imbalance between the 
      expression of this proteolytic enzyme and its inhibitors, which may contribute to 
      changes in the wound-healing process and ultimately lead to corneal ulcer 
      development.
CI  - Copyright 2002 Elsevier Science Ltd.
FAU - Ottino, Paulo
AU  - Ottino P
AD  - Department of Ophthalmology and Neuroscience Center of Excellence, Louisiana 
      State University Health Sciences Center, New Orleans, LA 70112, USA.
FAU - Taheri, Faramarz
AU  - Taheri F
FAU - Bazan, Haydee E P
AU  - Bazan HE
LA  - eng
GR  - EY04928/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Epithelium, Corneal/enzymology/*metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Matrix Metalloproteinase 9/genetics
MH  - Organ Culture Techniques
MH  - Plasminogen Activator Inhibitor 1/*genetics
MH  - Platelet Activating Factor/*pharmacology
MH  - Polymerase Chain Reaction/methods
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics
MH  - Tissue Inhibitor of Metalloproteinases/*genetics
EDAT- 2002/05/17 10:00
MHDA- 2002/07/20 10:01
CRDT- 2002/05/17 10:00
PHST- 2002/05/17 10:00 [pubmed]
PHST- 2002/07/20 10:01 [medline]
PHST- 2002/05/17 10:00 [entrez]
AID - S0014483501911352 [pii]
AID - 10.1006/exer.2001.1135 [doi]
PST - ppublish
SO  - Exp Eye Res. 2002 Mar;74(3):393-402. doi: 10.1006/exer.2001.1135.