Integrin expression during epidermal morphogenesis and wound healing

The integrins are a family of heterodimeric adhesion receptors expressed by virtually all cells. Integrins can bind cell and extracellular matrix ligands and are involved in signal transduction and migration. The epidermis, the outer protective covering of the body, consists of stratifiied keratinocytes attached to a basement membrane, primarily through integrins. As keratinocytes commit to terminal differentiation, they downregulate integrin function and leave the basement membrane. Our lab has previously shown that integrin dowregulation is an early, required event in commitment to terminal differentiation. In view of the importance of integrins, and their localization, integrins could be expected to play a role in the establishment and maintenance of the morphological organization of the epidermis. I have examined the pattern of integrin expression during the development of human epidermis and during healing of cutaneous blister wounds. During development of the epidermis, a single layer of keratinocytes progressively gives rise to multiple suprabasal layers of differentiated keratinocytes. The integrins expressed during development are the same as those in mature skin, but expression is temporally regulated and there are changes in distribution, especially at the onset of stratification. There are no apparent changes in ligand appearance or distribution. I have used skin organ culture to successfully reproduce these events in vitro. During healing of cutaneous suction blisters - in which keratinocytes must migrate to close the wound as well as re-establish the normal architecture - striking, strong suprabasal integrin expression during later stages of wound healing was detected, in contrast to the basally restricted pattern seen in unwounded epidermis. Suprabasal expression was also detected in psoriasis, a hyperproliferative disease. I have explored and discounted the possibility that inflammatory cytokines are responsible for this pattern. However, keratinocyte-fibroblast organotypic cultures do express integrins suprabasally, and provide a model for further analysis