title: 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 1.2 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.
  
  
  CONCLUSIONS
  These results suggest that PAI-2 has a role for promoting the differentiation of epidermal keratinocytes.
authors.affiliation: Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
authors.forename: Sunhyae
authors.initials: S
authors.lastname: Jang
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Yang
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: An
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Yoon
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Cho
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Ryu
authors.forename: Yeon-suk
authors.initials: YS
authors.lastname: Park
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Yoon
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
mesh_terms: D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000502:physiology; D006801:Humans; D053550:Keratin-10 / Q000032:analysis; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism*; D011498:Protein Precursors / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: C507493:KRT10 protein, human; D008565:Membrane Proteins; D017396:Plasminogen Activator Inhibitor 2; D011498:Protein Precursors; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C064554:loricrin; D053550:Keratin-10; C032253:involucrin; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human; D002118:Calcium