Posttranscriptional regulation of PAI-1 gene expression.

The plasminogen activator-plasmin cascade is involved in multiple physiological and pathological processes including fibrinolysis, wound healing, fibrosis, angiogenesis, embryo implantation and tumor cell invasion and metastasis. Plasminogen activator-inhibitor type 1 (PAI-1) is the major physiological regulator of plasminogen activation. PAI-1 is expressed in a variety of mammalian cells and is regulated by growth factors, cytokines and hormones, including agents that elevate cAMP levels. Although cyclic nucleotide regulation of PAI-1 is observed in diverse cell types in various species, including human, limited studies have addressed the mechanism of this regulation. Here we review our work on the regulation of PAI-1 mRNA degradation in HTC rat hepatoma cells, describing the cis-acting cAMP-responsive sequence in the transcript and a novel RNA binding protein that interacts with it. Potential mechanisms by which this RNA-binding protein may be involved in cyclic nucleotide regulation of mRNA stability are discussed and cAMP regulation of PAI-1 in other systems is summarized.