Fig. 8.

Schematic illustration of the regulation of matriptase-driven serine protease network by inflammation in skin diseases. A matriptase-driven serine protease network, comprised of matriptase as the initiator protease, prostasin, a downstream protease substrate of matriptase, and HAI-1, a Kunitz-type serine protease inhibitor, is expressed at high levels at the cell surface of living keratinocytes in normal skin, where the activation of the system is tightly regulated. In some skin disease with inflammation, proinflammatory cells are recruited that release reactive oxygen species (ROS) and increase tissue acidity. Both the ROS and acidity stimulate nearby keratinocytes to activate matriptase. The active matriptase rapidly activates prostasin before the inhibitor HAI-1 forms complexes with the active matriptase and active prostasin.