Localization of Plasminogen Activator Inhibitor Type 2 (PAI-2) in Hair and Nail: Implications for Terminal Differentiation

Abstract

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.

The plasminogen activator inhibitor-2 gene is not required for normal murine development or survival

“…Recent studies of PAI-2 gene expression have suggested that this protein may be required for specific steps in hair and skin development in the mouse (41). It is also a major component of the heavily cross-linked cornified envelope formed during the final stages of epidermal keratinocyte differentiation (42).…”

Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells

“…The shared expression of K6 by the companion layer and the niche has led to the investigation of potential similarities and differences among these populations of cells and raised the issue of whether there is a shared lineage relationship (Higgins et al, 2009). In fact, K6-expressing cells in telogen and anagen, as well as the cells surrounding the club hair in catagen, share a common molecular signature [expression of K6 (Winter et al, 1998;Wang et al, 2003;Hsu et al, 2011), PAI-2 (Lavker et al, 1998), calretinin (Poblet et al, 2005) and S100A6 (Ito and Kizawa, 2001)]. The companion layer is composed of thin long cells adjacent to the IRS, whereas the K6 + niche (and catagen K6 + ) cells are cuboidal (Hsu et al, 2011).…”

“…The K6 + layer is thought to share similarities with segments of the companion layer of anagen HFs (Higgins et al, 2009); both are adjacent to the ORS and express K6 (Winter et al, 1998;Wang et al, 2003;Hsu et al, 2011), plasminogen activator inhibitor 2 (PAI2) (Lavker et al, 1998), calretinin (Poblet et al, 2005) and S100 calcium-binding protein A6 (S100A6) (Ito and Kizawa, 2001). However, the lineage relationship between the K6 + inner bulge and companion layers remains a mystery.…”

Identification of a Cytosolic NADP+-dependent Isocitrate Dehydrogenase That Is Preferentially Expressed in Bovine Corneal Epithelium

“…RNA probes were prepared using 35 S-labeled UTP. In situ hybridization was conducted as described (24).…”