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 proteinase inhibitor in that it is largely retained within the cell and is found in high concentrations in the upper viable layers of human epidermis. Studies using transfected cell lines that express high levels of PAI-2 have suggested that this inhibitor may confer protection against programmed cell death. To test the hypothesis that PAI-2 may protect 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 nature of the follicular epithelium makes it ideal for studying sequential stages of cell differentiation and death. PAI-2 mRNA and protein were detected in the differentiating cells of the outer root sheath and medulla of the follicle during the anagen phase of the hair growth cycle. PAI-2 was also detected in the permanent portion of the catagen follicle. In the telogen phase of the hair growth cycle, PAI-2 was limited to the postmitotic cells of the outer root sheath directly abutting the club hair. In the nail, PAI-2 was detected in the differentiating cells of the matrix and nail bed. This consistent, selective distribution of PAI-2 in the postmitotic, maturing cells prior to terminal keratinization and death suggests that (i) PAI-2 may be considered as a differentiation marker for many epithelial cell types, and (ii) PAI-2 is appropriately positioned to protect epithelial cells from premature demise.