Differentiating cells of murine stratified squamous epithelia constitutively express plasminogen activator inhibitor type 2 (PAI-2).
In stratified squamous epithelia a critical balance among cell proliferation, differentiation, and death must be maintained in order for these tissues to fulfill their barrier function. Previous studies have demonstrated that plasminogen activator inhibitor 2 (PAI-2) is a product of differentiating epidermal keratinocytes, suggesting a role for this inhibitor during squamous differentiation. Furthermore, in certain tumor cell lines, overexpression of PAI-2 confers resistance to the induction of programmed cell death, suggesting cytoprotective function(s). In the present study we demonstrate that PAI-2 mRNA and protein are constitutively and uniquely expressed in differentiating cells of murine stratified squamous epithelia, including epidermis, esophagus, vagina, oral mucosa, and tongue. PAI-2 immunohistochemical localization patterns suggest a predominantly cytosolic distribution, consistent with biochemical identification of the major PAI-2 species as a 43-kDa, presumably non-glycosylated protein. Functional analysis shows that the majority of epithelial PAI-2 is active. In contrast to the high levels of PAI-2 expression in stratified squamous epithelia, little or no PAI-2 is detectable in simple epithelia. These findings suggest that epithelial PAI-2 may mediate inhibition of intracellular proteinases associated with events during terminal differentiation and death that are unique to stratified squamous epithelia.
Risse
B C
BC
Department of Dermatology, University of Pennsylvania, Philadelphia 19104-6142, USA.
Brown
H
H
Lavker
R M
RM
Pearson
J M
JM
Baker
M S
MS
Ginsburg
D
D
Jensen
P J
PJ
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D004817:Epidermis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism; D005260:Female; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018632:Mice, Inbred SENCAR; D009061:Mouth Mucosa / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*; D014059:Tongue / Q000378:metabolism; D014621:Vagina / Q000378:metabolism
D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors