Hyaluronan suppresses epidermal differentiation in organotypic cultures of rat keratinocytes
Hyaluronan suppresses epidermal differentiation in organotypic cultures of rat keratinocytes
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DOI：
10.1016/j.yexer.2004.01.031
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发表时间：
2004-06-10
影响因子：
3.7
通讯作者：
Maytin, EV
中科院分区：
文献类型：
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作者：
Passi, A;Sadeghi, P;Maytin, EV
透明质酸（hyaluronic acid， HA）是体内表皮角质形成细胞间丰富的基质成分，但其在体内的功能尚不清楚。我们使用升降培养模型，其中大鼠表皮角质形成细胞（REKs）在气液界面分层，以了解透明质酸是否可能调节表皮增殖和/或分化。在这个模型中，分化的早期标记（角蛋白10）和后期标记（聚侧蛋白、角透明素颗粒、角化层）在时间和空间上都得到了忠实的表达。使用两种不同的分析技术测量的透明质酸，只有在密封表皮隔室的完整基底膜存在的情况下才会积累到高水平。为了测试HA是否在分化中具有功能作用，在分层时间过程实验中，每天添加透明质酸链霉菌酶（Streptomyces hyaluronidase, 1 U/ml，在4 h内消化95%的HA）来提升培养物，持续5天。在streph处理的培养中，通过半定量组织学分析，与对照组相比，profilaggrin的表达以及角透明素颗粒的数量和大小显著增加。Western分析证实了K10蛋白和聚丝蛋白/聚丝蛋白与streph相关的积累。因此，表皮细胞间透明质酸的存在似乎对角化细胞分化过程中发生的细胞内事件起到了抑制作用。(C) 2004爱思唯尔公司版权所有。
Hyaluronan (hyaluronic acid, HA) is an abundant matrix component between keratinocytes of the epidermis in vivo, but its function there remains unclear. We used a lift culture model, in which rat epidermal keratinocytes (REKs) stratify at an air-liquid interface, to ask whether HA may regulate epidermal proliferation and/or differentiation. In this model, early markers of differentiation (keratin 10), and later markers (profilaggrin, keratohyalin granules, cornified layers) are faithfully expressed, both temporally and spatially. HA, measured using two different analytical techniques, accumulated to high levels only in the presence of an intact basement membrane that seals the epidermal compartment. To test whether HA has a functional role in differentiation, Streptomyces hyaluronidase (StrepH, I U/ml; digests >95% of HA within 4 h) was added daily to lift cultures during stratification time-course experiments over 5 days. In StrepH-treated cultures, the expression of profilaggrin and the number and size of keratohyalin granules were significantly increased relative to controls using semiquantitative histological analyses. The StrepH-related accumulation of K10 protein and profilaggrin/filaggrin were confirmed by Western analyses. Thus, it appears that the presence of intercellular HA in the epidermis acts as a brake upon intracellular events that occur during keratinocyte differentiation. (C) 2004 Elsevier Inc. All rights reserved.