LOCALIZATION OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-2 (PAI-2) IN HAIR AND NAIL - IMPLICATIONS FOR TERMINAL DIFFERENTIATION

Plasminogen activator inhibitor type 2 (PAI-2) is an unusual serine pr oteinase inhibitor in that it is largely retained within the cell and is found in high concentrations in the upper viable layers of human ep idermis, Studies using transfected cell lines that express high levels of PAI-2 have suggested that this inhibitor may confer protection aga inst programmed cell death. To test the hypothesis that PAI-2 may prot ect epithelial cells in vivo from premature programmed cell death, we determined expression patterns of PAI-2 in murine hair and nail. These epidermal derivatives are comprised of numerous epithelial cell types with distinct differentiation pathways. Furthermore, the cyclic natur e of the follicular epithelium makes it ideal for studying sequential stages of cell differentiation and death. PAI-2 nRNA and protein were detected in the differentiating cells of the outer root sheath and med ulla of the follicle during the anagen phase of the hair growth cycle. PAI-2 was also detected in the permanent portion of the catagen folli cle. In the telogen phase of the hair growth cycle, PAI-2 was limited to the postmitotic cells of the outer root sheath directly abutting th e club hair. In the nail, PAI-2 was detected in the differentiating ce lls of the matrix and nail bed. This consistent, selective distributio n of PAI-2 in the postmitotic, maturing cells prior to terminal kerati nization and death suggests that (i) PAI-2 may be considered as a diff erentiation marker for many epithelial cell types, and (ii) PAI-2 is a ppropriately positioned to protect epithelial cells from premature dem ise.