EXPRESSION OF INTEGRINS AND BASEMENT-MEMBRANE COMPONENTS BY WOUND KERATINOCYTES

EXPRESSION OF INTEGRINS AND BASEMENT-MEMBRANE COMPONENTS BY WOUND KERATINOCYTES
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DOI:
10.1172/jci116719
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发表时间:
1993-09-01
影响因子:
15.9
通讯作者:
HEINO, J
HEINO, J
中科院分区:
医学1区
文献类型:
--
作者:
LARJAVA, H;SALO, T;HEINO, J

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细胞外基质蛋白及其细胞受体整合素在角化细胞粘附和迁移中起着重要作用。在伤口愈合过程中,角化细胞分离,迁移,直到两个上皮膜对峙,然后再生基底膜。我们检测了在人粘膜伤口愈合过程中不同整合素及其推定配体在角质形成细胞中的表达。迁移的角化细胞持续表达kalinin,但不表达基底膜带的其他典型成分:IV型胶原、层粘连蛋白和VII型胶原。当上皮层相互对峙时,这些缺失的基底膜成分开始逐渐在整个伤口区域出现。在迁移过程中,角化细胞中整合素β 1亚基的表达增加。与β 1相关的α 2和α 3亚基在创面角化细胞中持续表达,而α 5亚基仅在再上皮过程中存在于角化细胞中。此外,迁移细胞开始表达α (v)-整合素,这在未受影响的上皮中不存在。所有角质形成细胞在迁移过程中也表达了α 6beta4整合素。在迁移细胞中,整合素的分布发生了改变。在正常粘膜中,β -整合素主要位于外侧质膜上,而在未受影响的组织中,α - 6β - 4主要位于基底角质形成细胞的基底表面。在伤口中,整合素存在于迁移角化细胞的丝状伪足中,也存在于迁移片若干细胞层的周围细胞中。结果表明,迁移的角质形成细胞在人深部伤口中增加了其整合素库。整合素表达的变化与基底膜组成的变化同时发生,表明这两组分子在伤口愈合过程中密切相互作用。
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 beta1 subunit was increased in keratinocytes during migration. The beta1-associated alpha2 and alpha3 subunits were expressed constantly by wound keratinocytes whereas the alpha5 subunit was present only in keratinocytes during reepithelialization. Furthermore, migrating cells started to express alpha(v)-integrins which were not present in the nonaffected epithelium. All keratinocytes also expressed the alpha6beta4 integrin during migration. In the migrating cells, the distribution of integrins was altered. In normal mucosa, beta1-integrins were located mainly on the lateral plasma membrane and alpha6beta4 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.