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Medientyp:
E-Artikel
Titel:
The potential for localized translation and induction of plasminogen activator inhibitor‐1 at the myoendothelial junction in response to TNF‐alpha
Beschreibung:
<jats:sec><jats:label /><jats:p>The myoendothelial junction (MEJ) is a signaling microdomain that integrates endothelial cells (EC) and vascular smooth muscle cells (VSMC). We have demonstrated that plasminogen activator inhibitor‐1 (PAI‐1) is enriched at the MEJ and functions to regulate MEJ formation, which suggests the localization of PAI‐1 at the MEJ is deliberate. To determine if PAI‐1 expression at the MEJ is inducible, we applied the inflammatory cytokine TNF‐α to our in vitro MEJ model (VCCC) and using qRT‐PCR show increased PAI‐1 mRNA at the MEJ. Transmission electron microscopy of MEJs from three microvascular beds demonstrates a large quantity of ribosomes, suggesting mRNA may target to the MEJ for localized translation. We next used PAI‐1 specific ELISAs and show a 4‐fold increase in total PAI‐1 and active PAI‐1 at the MEJ as compared to EC or VSMC, implying the PAI‐1 mRNA at the MEJ is maintained in a stable condition to allow for rapid translation. To elucidate the mechanism of PAI‐1 mRNA stabilization, we determined the expression of PAI‐1 RNA binding protein, serine binding protein‐1 (SERBP1) using immunoblotting and confocal microscopy of VCCC fractions, finding it to be expressed at the MEJ. Based on these data, we conclude that during an inflammatory response increased PAI‐1 expression at the MEJ may be due to stabilization of PAI‐1 mRNA by SERBP1. Supported by NIH RO1 088554 and an AHA SDG.</jats:p></jats:sec>