A Primary Study On The Expression And Function Of Plasminogen Activator Inhibitor-3(PAI-3) In The Epithelization Of Human Skin

Skin lies in the interface between inner condition and outer environment of body is an important protective organ as a barrier and the epidermis is mostly made of keratinocytes.Proteinases is the important regulator in the epithelization of skin.PAI-3,also called protein c inhibitor, is a main member of cascade of plasminogen activators and their inhibitors.It has been recently showed that PAI-3,expressed in varies of organs and tisues,such as liver,pancreas,urinary and reproductive system and platelet and so on,has significant role in hemostasis,fibrinolysis,cell movement,reproduction and metastasis and invasion of tumor.However,up to now,these is no report on the expression and role of PAI-3 in the epithelization of human skin. In this study,the expression and role of PAI-3 in the epithelization of human skin,including normal adult human skin,cultured differentiated keratinocytes and the development of human embryo,were observed,so as to elucidate the possible role of PAI-3 in the epithelization of skin and provide the experimental base for further studying the mechanism in epithelization of skin and all kinds of skin diseases. Methods: Three aspects were studied in the epithelization of skin of PAI-3 with the techniques of Immunohistochemistry (IHC),Immunocytochemistry (ICC),RT-PCR and the analysis of PAI-3 in cornified envelope.First,the expression and role of PAI-3 were examined in the normal adult skin;second,the expression and role of PAI-3 were detected in the cultured differentiated keratinocytes;at last,the expression of PAI-3 was observed in the development of huam embryo. Results: PAI-3 was mainly expressed in differentiated keratinocytes of the epidermis in normal adult skin. PAI-3 was incorporated into the cornified envelope of terminally differentiated keratiocytes. The expression of PAI-3 and PAI-3 mRNA were accordingly increased with the enhancement of differentiated KCs cultured with high calcium and decreased in the late phase. PAI-3 was mainly located in the nuclear membrane in KCs cultured in low calcium,however,in high calcium mostly in cytoplasm. PAI-3 was mainly expressed in the superficial , more differentiatied layers of the epidermis and exhibited a very high expression in the development of embryonic period,with the highest level in the middle embryonic phase while decreased in the late human embryonic stage. PAI-3 mRNA was strongly expressed in the development of embryonic period,with the highest level in the middle embryonic phase while still kept a rather high level in the late human embryonic stage. Conclusion: PAI-3 was expressed in the human skin and mainly located in the superficial,more differentiatied layers of the epidermis,and was incorporated into the cornified envelope of terminally differentiated keratiocytes. The expression of PAI-3 and PAI-3 mRNA were accordingly increased with the enhancement of differentiated KCs and transfered from nuclear membrane in low calcium to cytoplasm in the high calcium. PAI-3 exhibited a very high expression in the development of embryonic period,with the highest level in the middle embryonic phase. PAI-3 may be related to the differentiation of keratinocytes and has concernful role in the epithelization of skin.