Extracellular matrix proteins and their cellular receptors, integrins, play a fundamental role in keratinocyte adhesion and migration. During wound healing, keratinocytes detach, migrate until the two epithelial sheets confront, and then regenerate the basement membrane. We examined the expression of different integrins and their putative ligands in keratinocytes during human mucosal wound healing. Migrating keratinocytes continuously expressed kalinin but not the other typical components of the basement membrane zone: type IV collagen, laminin, and type VII collagen. When the epithelial sheets confronted each other, these missing basement membrane components started to appear gradually through the entire wound area. The expression of integrin 81 subunit was increased in keratinocytes during migration. The #,B-associated a2 and a3 subunits were expressed constantly by wound keratinocytes whereas the a5 subunit was present only in keratinocytes during reepithelialization. Furthermore, migrating cells started to express a,-integrins which were not present in the nonaffected epithelium. All keratinocytes also expressed the a684 integrin during migration. In the migrating cells, the distribution of integrins was altered. In normal mucosa, ,61-integrins were located mainly on the lateral plasma membrane and aQ84 at the basal surface of basal keratinocytes in the nonaffected tissue. In wounds, integrins were found in filopodia of migrating keratinocytes, and also surrounding cells in several cell layers of the migrating sheet. The results indicate that migrating keratinocytes in deep human wounds enlarge their integrin repertoire. The changes in integrin expression take place concomitantly with changes in the basement membrane composition, suggesting a close interplay of these two groups of molecules during wound healing. (J. Clin. Invest. 1993. 92:1425-1435

Cell adhesion receptors of the integrin family play a major role during re-epithelialization of human wounds. We have previously documented that the expression of alpha v family integrins is induced in keratinocytes of mucosal wounds [1]. In the present investigation, we extended these studies to determine whether alpha v beta 6 integrin is expressed during wound healing in humans. Mucosal and epidermal wound sections from 1- to 7-day-old wounds were used for immunolocalization of integrins and their putative ligands. In addition, freshly isolated epidermal keratinocytes were used to study integrin expression in vitro. Expression of alpha v beta 6 integrin appeared relatively late during mucosal and dermal wound healing. Maximal expression was seen in 7-day-old wounds in which epithelial sheets had fused and granulation tissue was present. Fibronectin and tenascin, both possible ligands for alpha v beta 6 integrin, were found concentrated underneath the basal epithelial cells expressing this receptor, and the maximal expression of tenascin coincided with that of alpha v beta 6 integrin. Freshly isolated epidermal keratinocytes did not stain for alpha v beta 6 integrin but began to express this integrin after subculturing. Our results suggest that the expression of alpha v beta 6 integrin, a putative binding integrin for fibronectin and tenascin, is induced in keratinocytes when epithelial sheets fuse during wound healing.

Proteoglycans (PGs) function in regulating aspects of cell behavior, such as proliferation, adhesion, and migration. In this report, we investigated the localization of three heparan sulphate PGs (basement membrane [BM] heparan sulphate PG, CD44, and syndecan-1) and two small dermatan/chondroitin sulphate PGs (decorin and biglycan) in chronically inflamed human periodontium. Frozen sections were analyzed by immunofluorescence microscopy. In inflamed tissue, BM heparan sulphate PG showed reduced immunostaining in subepithelial and subendothelial basement membrane. Loss of CD44 and syndecan-1 was common in epithelial cells of inflamed periodontal tissue. Suprabasal keratinocytes of epithelium expressed involucrin, a cornified envelope protein and marker for epithelial differentiation, while the expression of syndecan-1 was weak or absent. In contrast, expression of the mesenchymal variant of CD44 and syndecan-1 was strong in infiltrating lymphocytes. Small dermatan/chondroitin sulphate PGs, decorin and biglycan, were also present in markedly reduced amounts in the periodontal connective tissue in chronic inflammation. In addition, decorin localized in the connective tissue along short rod-like structures. The results suggest that proteoglycan-dependent intercellular adhesion of keratinocytes is decreased and that adhesion of lymphocytes to matrix molecules via cell surface PGs increased in chronic inflammation. Disappearance of adhesion-modulating small dermatan/chondroitin sulphate PGs may further regulate cell migration in inflamed periodontium.

Periodontal epithelium plays a critical role in protection, destruction and repair of human periodontium. During optimal repair, epithelium migrates and covers the wound surface to prevent infection and damage of the vulnerable underlying connective tissue. During periodontal destruction, junctional epithelium undergoes transformation to pocket epithelium that has quite different characteristics from junctional epithelium. In the course of periodontal disease the epithelial attachment to the tooth surface is lost and the epithelium proliferates and extends pseudo‐rete ridges deep into the inflamed connective tissue. Both scenarios, repair and destruction, involve active epithelial migration either in the wound provisional matrix or in the inflamed connective tissue matrix, respectively. This review covers recent research data on cellular receptors, integrins, that mediate epithelial cell migration during wound healing and destruction of human periodontiurn.