Keratinocyte migration, proliferation, and differentiation in chronic ulcers from patients with diabetes and normal wounds
Keratinocyte migration, proliferation, and differentiation in chronic ulcers from patients with diabetes and normal wounds
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DOI：
10.1369/jhc.2008.951194
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发表时间：
2008-07-01
影响因子：
3.2
通讯作者：
Olerud, John E.
中科院分区：
文献类型：
--
作者：
Usui, Marcia L.;Mansbridge, Jonathan N.;Olerud, John E.
正常I型急性伤口的上皮化通过一系列有序的事件发生，由此角质形成细胞迁移、增殖和分化以恢复屏障功能。慢性溃疡表皮中的角质形成细胞不能执行这一系列事件。为了更好地了解慢性溃疡的上皮动力学，我们使用免疫组织化学来评估糖尿病患者慢性溃疡边缘角质形成细胞沿着的增殖、分化、粘附和迁移。我们将这些特征与正常志愿者急性切口和切除伤口的迁移上皮舌的角质形成细胞进行了比较。慢性溃疡边缘的角化细胞高度增殖（Ki 67增殖标志物），具有活化表型（K16），不对参与表皮分化的角蛋白染色（K10和K2），并显示LM-3A 32（未切割，层粘连蛋白5 α 3链的前体）表达减少，LM-3A 32是迁移上皮上存在的关键分子。相反，正常急性伤口移行上皮中的角质形成细胞不表达增殖标记物Ki 67，但表达K10、K2和LM-3A 32。更好地了解角质形成细胞迁移的分子机制可能会导致受损伤口愈合治疗的分子靶点。
Epithelialization of norma I 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 alpha 3 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.