Laminin-5 inhibits human keratinocyte migration

被引:110
作者
OToole, EA
Marinkovich, MP
Hoeffler, WK
Furthmayr, H
Woodley, DT
机构
[1] NORTHWESTERN UNIV,DEPT DERMATOL,SCH MED,CHICAGO,IL 60611
[2] STANFORD UNIV,SCH MED,DEPT DERMATOL,PALO ALTO,CA 94305
[3] STANFORD UNIV,SCH MED,DEPT PATHOL,PALO ALTO,CA 94305
[4] VA PALO ALTO HLTH CARE SYST,DERMATOL SERV,PALO ALTO,CA 94304
关键词
D O I
10.1006/excr.1997.3586
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Laminin-5 (previously known as kalinin, epiligrin, and nicein) is an adhesive protein localized to the anchoring filaments within the lamina lucida space of the basement membrane zone lying between the epidermis and dermis of human skin, Anchoring filaments are structures within the lamina lucida and lie immediately beneath the hemidesmosomes of the overlying basal keratinocytes apposed to the basement membrane zone, Human keratinocytes synthesize and deposit laminin-5. Laminin-5 is present at the wound edge during reepithelialization, In this study, we demonstrate that laminin-5, a powerful matrix attachment factor for keratinocytes, inhibits human keratinocyte migration. We found that the inhibitory effect of laminin-5 on keratinocyte motility can be reversed by blocking the alpha 3 integrin receptor. Laminin-5 inhibits keratinocyte motility driven by a collagen matrix in a concentration-dependent fashion. Using antisense oligonucleotides to the alpha 3 chain of laminin-5 and an antibody that inhibits the cell binding function of secreted laminin-5, we demonstrated that the endogenous laminin-5 secreted by the keratinocyte also inhibits the keratinocyte's own migration on matrix. These findings explain the hypermotility that characterizes keratinocytes from patients who have forms of junctional epidermolysis bullosa associated with defects in one of the genes encoding for laminin-5 chains, resulting in low expression and/or functional inadequacy of laminin-5 in these patients. These studies also suggest that during reepithelialization of human skin wounds, the secreted laminin-5 stabilizes the migrating keratinocyte to establish the new basement membrane zone. (C) 1997 Academic Press.
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页码:330 / 339
页数:10
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