Matriptase connects the coagulation cascade to epithelial signaling and proteolysis. Schematic representation of how matriptase amplifies coagulation factor signaling in epithelia. The results of this study suggest that FVIIa and FXa both directly activate matriptase, which in turn activates PAR2 and processes other epithelial substrates. This may connect coagulation activation to epithelial remodeling. Matriptase also mediates PAR2 signaling by the epithelial MASPs hepsin and prostasin. Additional cofactors such as EPCR may support PAR2 activation by the TF:FVIIa:FXa ternary complex, and at high concentrations, FXa may directly activate PAR2 without matriptase transactivation.