Alteration of Integrin Expression in Migrating Epidermal Cells and Analysis of Extracellular Matrix Proteins in the Dermis with Chronic Wounds

再上皮化失败是慢性创伤的病理生理特征。然而，这种失败的机制尚未完全阐明。在急性创面再上皮化过程中，迁移的表皮细胞上调整合素α5 β1、αvβ5、αvβ6的表达，这些整合素在急性创面再上皮化过程中发挥重要作用。层粘连蛋白-1是基底膜成分，出现在再上皮化过程的后期。本研究以6例烧伤患者（急性创面，对照）和11例压疮患者标本为样本，采用免疫组化方法检测迁移表皮α5β1、真皮-表皮交界处层粘连蛋白-1和真皮纤维连接蛋白的表达。然后将α5β1与组织学、层粘连蛋白-1和纤维连接蛋白的分布结果进行比较。11例压疮标本中有8例α5β1表达明显降低或呈阴性，对照组α5β1表达明显升高。表达的程度与伤口表面表皮伸长的组织学表现密切相关。此外，所有压疮标本中纤维连接蛋白的分布都明显下降，而6例烧伤标本中有3例纤维连接蛋白的分布增加。在烧伤（对照组）和压疮标本中，细胞α5β1阳性染色距离与层粘连蛋白-1阴性染色距离之间存在显著的统计学相关性。我们的数据表明，α5β1表达的减少与慢性伤口（压疮）的再上皮化失败有关。在大鼠急性创面模型中，我们采用免疫组化方法检测了α5β1的表达时间，并将α5β1的表达与组织学、真皮表皮交界处层粘连蛋白-1的表达以及真皮中纤维连接蛋白的分布进行了比较。α5β1在溃疡形成后第1天开始在迁移的表皮细胞上表达，并在第4天呈升高趋势，此时表皮细胞沿真皮层表面移动。迁移的表皮细胞到达肉芽组织后，α5β1暂时降低。第14天再次升高，第21天伤口愈合后变为负值。我们还测量了迁移表皮细胞α5β1（基底上表达）阳性染色和层粘连蛋白-1阴性染色的距离。第1天检测到真皮纤维连接蛋白，第7天达到峰值，随后下降。α5β1的表达与真皮纤维连接蛋白的分布无统计学相关性。因此，我们的数据表明，α5β1的基底上表达是表皮细胞迁移的一个指标

Failure of re- eplthelialization characterizes the pathophysiology of chronic wounds. However, the mechanism of this failure has not been fully clarified. During the re- epithelialization of acute wounds, migrating epidermal cells up- regulate integrins α5 β1, αvβ5, αvβ6 and these integrins play an important role in the re- eplthelialization process. Laminin-1 is a basement membrane component which appears during the late phase of the re- eplthelialization process. In this study, with 6 specimens from burn patients (acute wounds, control) and 11 specimens from patients with pressure ulcers, we examined the expression of α5β1 in the migrating epidermis, laminin-1 at the dermal-epidermal junction and fibronectin in the dermis by an immunohistochemical method. We then compared the findings for α5β1 with histological, laminin-1 and fibronectin distribution findings. In 8 out of the 11 pressure ulcer specimens, the expression of α5β1 significantly decreased or was negative while it increase … More d in the control. The degree of expression correlated well with histological findings of epidermal elongation over the wound bed. Moreover, fibronectin distribution in all the pressure ulcer specimens decreased considerably while it increased in 3 out of the 6 burn specimens. A statistically significant correlation was found beween the distance at which the cells were positively stained for α5β1 and the distance at which they were negatively stained for laminin-1 in both the burn (control) and pressure ulcer specimens. Our data demonstrated that the decrease in α5β1 expression correlated with the failure in re-epithelialization of chronic wounds (pressure ulcers). It was also suggested that the decrease in fibronectin distribution was responsible for the failure of the re-epithelialization processIn a rat acute wound model we examined the time course of α5β1 expression using an immunohistochemical method, and compared the findings of α5β1 expression with histological findings, the expression of laminin-1 at the dermal0epidermal junction, and the distribution of fibronectin in the dermis. Expression of α5β1 on migrating epidermal cells was detected from the first day after ulcer formation, and it increased until the fourth day during which time the epidermal cells moved along the surface of the dermis. After the migrating epidermal cells reached granulation tissue, α5β1 decreased temporarily. Then it increased again on day 14, and it became negative with wound closure on day 21. We also measured the distance at which the migrating epidermal cells stained positively for α5β1 (suprabasal expression) and negatively for laminin-1. Fibronectin in the dermis was detected on the first day, peaked on the seventh day, and then decreased. There was no statistical correiation between the α5β1 expression and the distribution of dermal fibronectin. Thus, our data demonstrated that suprabasal expression of α5β1 is an indicator of epidermal cell migration Less