Role of plasminogen activator inhibitor-2 (PAI-2) in keratinocyte differentiation

Abstract: Background: Plasminogen activator inhibitor-2 (PAI-2) is an enzyme inhibitor which is involved in various biological processes including cell differentiation, tissue regrowth and regeneration. Although PAI-2 has been originally isolated as an extracellular inhibitor of urokinase plasminogen activator (uPA), recent studies indicate that PAI-2 has other intracellular effects in keratinocyte, such as the component of cornified envelope. Objective: The aim of this study is to investigate the expression and functional role of PAI-2 during the keratinocyte differentiation. Methods: We transduced keratinocytes with adenovirus harboring the expression cassette for PAI-2, then examined the effect on keratinocytes differentiation. Results: When cultured epidermal keratinocytes were treated with 1.2mM calcium, PAI-2 expression was increased time-dependently at both mRNA and protein levels. The calcium-induced PAI-2 expression was abolished by treatment with p38 MAPK inhibitor, while overexpression of MKK6 led to the increase of PAI-2 expression. When PAI-2 was overexpressed by adenoviral transduction, the expression of keratinocyte differentiation markers such as involucrin, keratin 10 and loricrin was markedly increased. Concomitantly, overexpression of PAI-2 resulted in the retardation of cell growth, with the increase of Rb and p53. Conclusion: These results suggest that PAI-2 has a role for promoting the differentiation of epidermal keratinocytes. [Copyright &y& Elsevier]