Anti‐integrin antibodies induce type IV collagenase expression in keratinocytes
Anti‐integrin antibodies induce type IV collagenase expression in keratinocytes
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DOI：
10.1002/jcp.1041570125
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发表时间：
1993-10
影响因子：
5.6
通讯作者：
H. Larjava;J. Lyons;T. Salo;M. Mäkelä;L. Koivisto;H. Birkedal‐Hansen;S. K. Akiyama;K. Yamada;J. Heino
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文献类型：
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作者：
H. Larjava;J. Lyons;T. Salo;M. Mäkelä;L. Koivisto;H. Birkedal‐Hansen;S. K. Akiyama;K. Yamada;J. Heino
在伤口愈合过程中，细胞周蛋白水解被认为对于角质形成细胞从基底膜分离以及它们迁移到伤口床中至关重要。我们对人粘膜角质形成细胞中的整合素型细胞粘附/迁移受体进行了表征，并检查了它们在调节 IV 型胶原酶基因表达中的功能。 β1 类的两个主要整合素，α2β1 和 αβ1，被发现分别充当胶原蛋白和纤连蛋白受体。研究发现，针对 β1 和 α3 整合素亚基的抗体能够以剂量依赖性方式数倍地刺激 92 kDa IV 型胶原酶的表达。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联蛋白结合直接引起的，因为单独的抗 β1 抗体的 Fab 片段能够在不存在二级聚集抗体的情况下诱导胶原酶表达。抗 α2β1 整合素的抗体不会引起刺激。接种在不同基质（塑料、胶原、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相同的 IV 型胶原酶表达诱导。肽（GRGDS、GRGES）、蛋白质（纤连蛋白、层粘连蛋白、纤维蛋白原、白蛋白）或纤连蛋白抗体不能诱导 92 kDa IV 型胶原酶的表达。我们认为角质形成细胞周围的蛋白水解过程可以通过整合素型受体通过细胞外因子信号调节。 © 1993 Wiley-Liss, Inc.
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 β1 class, α2β1 and αβ1, were found to function as collagen and fibronectin receptors, respectively. Antibodies against β1 and α3 integrin subunits were found to stimulate the expression of the 92 kDa type IV collagenase severalfold in a dosedependent 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‐β1 antibodies alone were able to induce collagenase expression in the absence of secondary, clustering antibodies. Antibodies against α2β1 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. © 1993 Wiley‐Liss, Inc.