Laminin 5 deposition promotes keratinocyte motility.
Laminin 5 deposition promotes keratinocyte motility.
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层粘连蛋白 5 沉积促进角质形成细胞运动。
DOI：
10.1006/excr.1996.0280
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Kramer,RH
中科院分区：
文献类型：
--
作者：
Zhang,K;Kramer,RH
我们研究了个体整合素在促进人角质形成细胞迁移中的作用。在I型胶原或纤维连接蛋白包被的底物上的短期实验中，α2整合素抗体和α5整合素抗体分别阻断了迁移。出乎意料的是，整合素α3抗体也显著抑制细胞在这两种配体上的运动。时间过程免疫荧光染色显示，角质形成细胞的迁移伴随着内源性层粘连蛋白5的沉积。由于α3β1是这种配体的已知受体，这一观察结果表明，迁移的角化细胞在运动中使用新沉积的层粘连蛋白5。事实上，进一步的研究表明抗层粘连蛋白5阻断抗体能有效地抑制角质形成细胞在胶原和纤维连接蛋白底物上的运动。此外，细胞在层粘连蛋白5包被的底物上的迁移被抗α3和抗层粘连蛋白5抗体阻断。层粘连蛋白5在角化细胞的初始附着中似乎并不重要，因为细胞对I型胶原或纤维连接蛋白涂层表面的粘附不被α3整合素抗体或层粘连蛋白5抗体阻断，但分别可以被α2或α5抗体抑制。用anin体外伤试验，α3整合素和层粘连蛋白5的阻断抗体也阻断了脱落的单层再上皮。这些结果表明α3β1整合素通过与层粘连蛋白5的相互作用在角质形成细胞的迁移中起重要作用。此外，他们认为细胞迁移不仅依赖于外源性配体，更重要的是，依赖于内源性分泌的层粘连蛋白5。最后，这些数据与我们之前的发现一致，即在体内伤口愈合过程中，层粘连蛋白5是第一个由迁移的角质形成细胞表达和沉积的细胞外基质成分。
We examined the role of individual integrins in promoting human keratinocyte migration. In short-term assays on collagen type I- or fibronectin-coated substrates, migration was blocked by antibody to the α2 integrin and the α5 integrin, respectively. Unexpectedly, antibodies to integrin α3 also significantly inhibited cell locomotion on both ligands. Time-course immunofluorescence staining revealed that keratinocyte migration was accompanied by deposition of endogenous laminin 5. Since α3β1 is a known receptor for this ligand, this observation suggested that migrating keratinocytes use freshly deposited laminin 5 in locomotion. Indeed, further investigation showed that anti-laminin 5 blocking antibodies effectively inhibited keratinocyte motility on both collagen and fibronectin substrates. Furthermore, cell migration on laminin 5-coated substrates was blocked by both anti-α3 and anti-laminin 5 antibodies. Laminin 5 did not appear important in the initial attachment of keratinocytes, since adhesion of cells to collagen type I- or fibronectin-coated surfaces was not blocked by antibody to α3 integrin or to laminin 5, but could be inhibited by antibody to α2 or α5, respectively. Using anin vitrowound assay, blocking antibodies to α3 integrin and to laminin 5 also blocked reepithelization of the denuded monolayer. These results show that α3β1 integrin plays an important role in the migration of keratinocytes via their interaction with laminin 5. Furthermore, they suggest that cell migration is dependent not only on exogenous ligands but, importantly, on endogenously secreted laminin 5. Finally, the data are consistent with our earlier finding that laminin 5 is the first extracellular matrix component to be expressed and deposited by migrating keratinocytes during wound healingin vivo[1].