M. Riewald | Semantic Scholar

The prototypical thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a role for this receptor cascade in protection from sepsis.

Results demonstrate that PAR1 activation on endothelial cells can have opposite biologic effects, reveal a role for cross-communication between the prototypical barrier-protective S1P and barrier-disruptive PAR1 pathway, and suggest that S 1P receptor-1 mediates protective effects of APC in systemic inflammation.

The concept that proinflammatory upstream coagulation protease signaling is mechanistically coupled and thus an integrated part of the TF–VIIa-initiated coagulating pathway, rather than a late event during excessive activation of coagulations and systemic generation of proteolytic activity, is supported.

Protease receptors are major determinants of the biological outcome of coagulation factor signaling on vascular cells, and are now recognized as an important aspect of the pro‐ and anti‐coagulant pathways.

Large scale gene expression profiling documented marked differences in both up- and down-regulated genes between APC and thrombin signaling in cytokine-stimulated cells, which may explain how APC can be therapeutically protective through the EPCR-PAR1 signaling despite ongoingThrombin generation due to disseminated intravascular coagulopathy.

Activated protein C mediates powerful cytoprotective effects through the protease‐activated receptor‐1 (PAR1) that translate into reduced harm in mouse injury models.

Not only PAR1, but also PAR2 can mediate barrier protection in endothelial cells and FXa can use either receptor to enhance barrier integrity, suggesting a potential protective effect of FXa and other agonists of endothelial PAR2, which should be explored in models of local and systemic inflammation in vivo.

Data suggest that an endothelial protein C receptor is expressed by lymphocytes whose activation with protein C or activated protein C arrests directed migration, which may be relevant for cytoprotective effects of the protein C pathway.

It is demonstrated that PAR-1 cleavage by Xa can elicit the same cellular response as thrombin, but mechanistic differences in receptor recognition may be crucial for specific roles for Xa in signaling during spatial or temporal separation from throm bin generation.

In vitro transcription and translation of the bomapin cDNA revealed the synthesis of an appropriately sized protein that was able to form SDS-stable complexes with thrombin and trypsin and raises the possibility that this serpin may play a role in the regulation of protease activities during hematopoiesis.