Usui Marcia L, Mansbridge Jonathan N, Carter William G, Fujita Mayumi, Olerud John E
Department of Medicine (Dermatology), University of Washington, 1959 NE Pacific Street, Box 356524, Seattle, WA 98195-6524, USA.
J Histochem Cytochem. 2008 Jul;56(7):687-96. doi: 10.1369/jhc.2008.951194. Epub 2008 Apr 14.
Epithelialization of normal acute wounds occurs by an orderly series of events whereby keratinocytes migrate, proliferate, and differentiate to restore barrier function. The keratinocytes in the epidermis of chronic ulcers fail to execute this series of events. To better understand the epithelial dynamics of chronic ulcers, we used immunohistochemistry to evaluate proliferation, differentiation, adhesion, and migration in keratinocytes along the margin of chronic ulcers from patients with diabetes mellitus. We compared these features with keratinocytes from the migrating epithelial tongues of acute incisional and excisional wounds from normal volunteers. Keratinocytes at the chronic ulcer edge are highly proliferative (Ki67 proliferation marker), have an activated phenotype (K16), do not stain for keratins involved in epidermal differentiation (K10 and K2), and show a reduced expression of LM-3A32 (uncleaved, precursor of the alpha3 chain of laminin 5), a key molecule present on migrating epithelium. In contrast, keratinocytes in normal acute wound migrating epithelium do not express the proliferation marker Ki67 but do express K10, K2, and LM-3A32. A better understanding of molecular mechanisms involved in keratinocyte migration may lead to molecular targets for therapies for impaired wound healing.
正常急性伤口的上皮化过程通过一系列有序事件发生，在此过程中角质形成细胞迁移、增殖并分化以恢复屏障功能。慢性溃疡表皮中的角质形成细胞无法执行这一系列事件。为了更好地理解慢性溃疡的上皮动力学，我们使用免疫组织化学方法评估糖尿病患者慢性溃疡边缘角质形成细胞的增殖、分化、黏附和迁移情况。我们将这些特征与正常志愿者急性切开和切除伤口迁移上皮舌中的角质形成细胞进行了比较。慢性溃疡边缘的角质形成细胞具有高增殖性（Ki67增殖标志物），具有活化表型（K16），不表达参与表皮分化的角蛋白（K10和K2），并且层粘连蛋白5α3链的未切割前体LM - 3A32的表达降低，LM - 3A32是迁移上皮上存在的关键分子。相比之下，正常急性伤口迁移上皮中的角质形成细胞不表达增殖标志物Ki67，但表达K10、K2和LM - 3A32。更好地理解角质形成细胞迁移所涉及的分子机制可能会为伤口愈合受损的治疗带来分子靶点。
