Protease-activated Receptor 1 signaling in lung injury

 In viral infections and after dsRNA inhalation, the extrinsic coagulation cascade is activated. Together with Dr. Mackman’s lab, we  found that the coagulation activation is mediated by lung epithelial cell expressed tissue factor (TF, FIII). Mice lacking TF in epithelial cells exhibit increased lung bleeding after viral infections or inhalation of dsRNA. Currently, we trying to understand how TF expression is regulated in the lung. Since TF leads to thrombin generation, we are also investigating the role of PAR1 in viral infections. PAR1 is known for its biased signaling after thrombin or activated protein C (APC) activation. Activation by thrombin leads to a proinflammatory phenotype whereas APC-PAR1 signaling is cytoprotective in endothelial cells. We found that PAR1 on endothelial cells contributes to lung inflammation after acute inhaled dsRNA possibly due to lack of APC signaling.