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Platelet-activating factor receptor. Gene structure and tissue-specific regulation

T Shimizu1, H Mutoh, S Kato

  • 1Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.

Advances in Experimental Medicine and Biology
|January 1, 1996
PubMed
Summary

The human platelet-activating factor receptor gene has two transcripts with different expression patterns. Transcript 1 is widely expressed and responds to inflammation, while Transcript 2 is tissue-specific and hormone-regulated.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Immunology

Background:

  • The human platelet-activating factor receptor (PAFR) gene is located on chromosome 1.
  • Two distinct 5'-noncoding exons (Exon 1 and 2) possess unique transcription initiation sites and promoters.

Purpose of the Study:

  • To investigate the alternative splicing and differential expression of PAFR gene transcripts.
  • To identify regulatory elements and hormonal influences on PAFR gene expression.

Main Methods:

  • Northern blotting to analyze transcript expression in various tissues and cells.
  • In vivo and in vitro transcriptional assays, including CAT reporter assays and gel mobility shift assays.

Main Results:

  • PAFR Transcript 1 shows ubiquitous expression, particularly in eosinophilic cells and leukocytes, and responds to inflammatory stimuli.

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  • PAFR Transcript 2 exhibits tissue-specific expression, absent in leukocytes and brain.
  • Hormonal treatments, including estrogen, retinoic acid (vitamin A), and thyroid hormone, differentially regulate PAFR expression, with specific hormone-responsive elements identified.
  • Conclusions:

    • Alternative splicing of the PAFR gene generates transcripts with distinct regulatory mechanisms and expression profiles.
    • Hormonal factors play a significant role in modulating PAFR expression, particularly for the tissue-specific transcript.
    • Understanding these regulatory pathways is crucial for comprehending PAFR's role in inflammatory and physiological processes.