1. Role of plasminogen activator inhibitor-2 (PAI-2) in keratinocyte differentiation.
- Author
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Jang S, Yang TH, An EJ, Yoon HK, Sohn KC, Cho AY, Ryu EK, Park YS, Yoon TY, Lee JH, and Kim CD
- Subjects
- Calcium metabolism, Epidermal Cells, Epidermis metabolism, Epidermis physiology, Humans, Keratin-10 analysis, Keratinocytes cytology, MAP Kinase Kinase 6 metabolism, Membrane Proteins analysis, Protein Precursors analysis, Retinoblastoma Protein analysis, Tumor Suppressor Protein p53 analysis, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, Cell Differentiation, Keratinocytes physiology, Plasminogen Activator Inhibitor 2 metabolism
- 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 1.2 mM 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 (c) 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2010
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