Fibroblasts facilitate re-epithelialization in wounded human skin equivalents
Fibroblasts facilitate re-epithelialization in wounded human skin equivalents
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DOI：
10.1038/labinvest.3700014
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发表时间：
2004-01-01
影响因子：
5
通讯作者：
Ponec, M
中科院分区：
文献类型：
--
作者：
El Ghalbzouri, A;Hensbergen, P;Ponec, M
伤口的再上皮化涉及角质形成细胞从伤口边缘的迁移。在此过程中，角质形成细胞的迁移和增殖将取决于角质形成细胞与真皮成纤维细胞和细胞外基质的相互作用。本研究旨在研究（1）成纤维细胞在再上皮化过程中的作用以及对真皮-表皮连接（DEJ）重建的作用和（2）再上皮化过程中的差异蛋白表达。对于这两个目的，使用三维人体皮肤等效物（HSE）。通过液氮冷冻在HSE中引入全层伤口，并通过手术刀线性切口引入浅表伤口。在不存在或存在外源性生长因子的情况下闭合伤口，随后监测DEJ的再上皮化和再生速率。在这项研究中获得的结果表明，成纤维细胞促进伤口闭合，但他们差异影响各种基底膜成分的沉积。与全层伤口相比，层粘连蛋白5在DEJ的沉积在浅表伤口中延迟。在冻伤过程中，一些基底膜（BM）成分仍然与真皮隔室，并可能促进BM重建。角质形成细胞生长因子的存在，尤其是表皮生长因子的存在加速了全层伤口而非浅表伤口的上皮再形成过程。此外，我们还研究了各种基底膜成分的沉积和蛋白质表达的差异，在一个横向扩展的表皮在未受伤的HSE。层粘连蛋白5，IV型和VII型胶原蛋白沉积在横向扩展的表皮中减少，表明这些蛋白质的存在不是体外发生角质形成细胞迁移所必需的。使用二维聚丙烯酰胺凝胶电泳，我们已经确定了DJ-1，蛋白质没有早期报道的不同表达过程中的上皮化的皮肤。
The re-epithelialization of the wound involves the migration of keratinocytes from the edges of the wound. During this process, keratinocyte migration and proliferation will depend on the interaction of keratinocytes with dermal fibroblasts and the extracellular matrix. The present study aimed to investigate ( 1) the role of fibroblasts in the re-epithelialization process and on the reconstitution of the dermal - epidermal junction (DEJ) and ( 2) differential protein expression during re-epithelialization. For both purposes, three-dimensional human skin equivalents (HSE) were used. A full-thickness wound in HSE was introduced by freezing with liquid nitrogen and a superficial wound by linear incision with a scalpel. The closure of the wound in the absence or presence of exogenous growth factors was followed by monitoring the rate of re-epithelialization and regeneration of the DEJ. The results obtained in this study demonstrate that fibroblasts facilitate wound closure, but they differentially affected the deposition of various basement membrane components. The deposition of laminin 5 at the DEJ was delayed in superficial wounds as compared to the full-thickness wounds. During freeze injury, some basement membrane ( BM) components remain associated with the dermal compartment and probably facilitate the BM reconstitution. The re-epithelialization process in full-thickness but not in superficial wounds was accelerated by the presence of keratinocyte growth factor and especially by epidermal growth factor. In addition, we have examined the deposition of various basement membrane components and the differences in protein expression in a laterally expanding epidermis in uninjured HSE. Laminin 5, type IV and VII collagen deposition was decreased in the laterally expanding epidermis, indicating that the presence of these proteins is not required for keratinocyte migration to occur in vitro. Using two-dimensional polyacrylamide gel electrophoresis, we have identified DJ-1, a protein not earlier reported to be differently expressed during the epithelialization process of the skin.