Role of plasminogen activator inhibitor-2 (PAI-2) in keratinocyte differentiation.
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.
Jang
Sunhyae
S
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
Yang
Tae Ho
TH
An
Eun Jeong
EJ
Yoon
Hyun Kyung
HK
Sohn
Kyung-Cheol
KC
Cho
Ah Young
AY
Ryu
Eun-Kyoung
EK
Park
Yeon-suk
YS
Yoon
Tae Young
TY
Lee
Jeung-Hoon
JH
Kim
Chang Deok
CD
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
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