"We observed that when we invalidated the expression of PAI-1, 16K PRL lost its antiangiogenic and antitumoral effects, which proves that the action of 16K PRL is a result of the intervention of PAI-1", Ingrid Struman reveals. These results have been published in the journal Nature Medicine(1). But, besides the discovery of the mediator of the known effects of 16K PRL, this study has allowed researchers to pinpoint another function of the 16K PRL fragment, which was completely unknown until now! “The identification of PAI-1 as the protein that binds the 16K PRL fragment has opened a completely new door to fibrinolysis", the scientist explains.

A new door opens on the functions of 16K PRL

As mentioned earlier, PAI-1 inhibits t-PA in order to halt the fibrinolysis process and therefore dissolve the blood clots formed during coagulation. Considering the role of PAI-1 in this process and its ability to bind 16K PRL, the researchers from Liège thought it would be a good idea to explore a possible function of this prolactin fragment in fibrinolysis.  “It’s something that was never explored before as we didn’t suspect any link between PAI-1 and 16K PRL”, the researcher continues. The tests for thrombosis carried out on mice models proved conclusive. “When we treated, with 16K PRL, mice in which a blood clot has been induced in the carotid artery, we observed that the clot disappeared far more quickly”, Ingrid Struman explains. “The 16K PRL fragment inhibits the PAI-1 protein and consequently, t-PA more efficiently dissolves the blood clots”, the scientist adds. This discovery is very interesting since there was no other known natural PAI-1 inhibitor until now...

Now they were on this path, Ingrid Struman’s team wanted to know exactly which regions of the 16K PRL prolactin fragment were responsible for inhibiting PAI-1. “We worked with smaller peptides from this fragment and we identified interesting regions. A patent was filed following this work”, the researcher says. In the mid or long term, depending on the efficacy and toxicity results of the tests on these peptides, they could be used in the treatment of thrombosis.

(1) Khalid Bajou, Stephanie Herkenne, Victor L Thijssen, Salvino D'Amico, Ngoc-Quynh-Nhu Nguyen, Ann Bouché, Sébastien Tabruyn, Mohammed Srahna, Jean-Yves Carabin, Olivier Nivelles, Cécile Paques, Ivo Cornelissen, Michelle Lion,     Agnès Noel, Ann Gils, Stefan Vinckier, Paul J Declerck, Arjan W Griffioen, Mieke Dewerchin, Joseph A Martial, Peter Carmeliet & Ingrid Struman. PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin. Nature Medicine (2014) doi:10.1038/nm.3552