Larjava H, Lyons J G, Salo T, Mäkelä M, Koivisto L, Birkedal-Hansen H, Akiyama S K, Yamada K M, Heino J
Department of Periodontics, University of Turku, Finland.
J Cell Physiol. 1993 Oct;157(1):190-200. doi: 10.1002/jcp.1041570125.
During wound healing, pericellular proteolysis is thought to be essential for the detachment of keratinocytes from basement membrane and in their migration into the wound bed. We have characterized integrin-type cell adhesion/migration receptors in human mucosal keratinocytes and examined their function in the regulation of type IV collagenase gene expression. Two major integrins of the beta 1 class, alpha 2 beta 1 and alpha 3 beta 1, were found to function as collagen and fibronectin receptors, respectively. Antibodies against beta 1 and alpha 3 integrin subunits were found to stimulate the expression of the 92 kDa type IV collagenase severalfold in a dose-dependent manner. Keratinocytes expressed also the 72 kDa type IV collagenase, the synthesis of which remained, however, unchanged in keratinocytes treated with anti-integrin antibodies. Stimulation of 92 kDa enzyme was found to be caused directly by antibody binding to integrins, since Fab-fragments of anti-beta 1 antibodies alone were able to induce collagenase expression in the absence of secondary, clustering antibodies. Antibodies against alpha 2 beta 1 integrin caused no stimulation. Keratinocytes seeded on different substrata (plastic, collagen, fibronectin, laminin, or vitronectin) showed equal induction of type IV collagenase expression. Expression of 92 kDa type IV collagenase could not be induced by peptides (GRGDS, GRGES), proteins (fibronectin, laminin, fibrinogen, albumin), or antibodies to fibronectin. We suggest that proteolytic processes around keratinocytes can be regulated by extracellular factors signalling through integrin-type receptors.
在伤口愈合过程中，细胞周围蛋白水解作用被认为对于角质形成细胞从基底膜脱离并迁移至伤口床至关重要。我们已对人黏膜角质形成细胞中的整合素型细胞黏附/迁移受体进行了表征，并研究了它们在调节IV型胶原酶基因表达中的功能。发现β1类的两种主要整合素，α2β1和α3β1，分别作为胶原蛋白和纤连蛋白受体发挥作用。发现针对β1和α3整合素亚基的抗体以剂量依赖性方式刺激92 kDa IV型胶原酶的表达数倍。角质形成细胞还表达72 kDa IV型胶原酶，然而在用抗整合素抗体处理的角质形成细胞中其合成保持不变。发现92 kDa酶的刺激是由抗体与整合素的结合直接引起的，因为单独的抗β1抗体的Fab片段能够在没有二级聚集抗体的情况下诱导胶原酶表达。针对α2β1整合素的抗体未引起刺激。接种在不同基质（塑料、胶原蛋白、纤连蛋白、层粘连蛋白或玻连蛋白）上的角质形成细胞显示出IV型胶原酶表达的同等诱导。92 kDa IV型胶原酶的表达不能由肽（GRGDS、GRGES）、蛋白质（纤连蛋白、层粘连蛋白、纤维蛋白原、白蛋白）或抗纤连蛋白抗体诱导。我们认为角质形成细胞周围的蛋白水解过程可由通过整合素型受体发出信号的细胞外因子调节。
