HYDROCORTISONE REGULATION OF HYALURONAN METABOLISM IN HUMAN SKIN ORGAN-CULTURE
HYDROCORTISONE REGULATION OF HYALURONAN METABOLISM IN HUMAN SKIN ORGAN-CULTURE
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DOI：
10.1002/jcp.1041640204
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发表时间：
1995-08-01
影响因子：
5.6
通讯作者：
TAMMI, R
中科院分区：
文献类型：
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作者：
AGREN, UM;TAMMI, M;TAMMI, R
我们研究了氢化可的松(HC)对人皮肤外植体透明质酸(HA)代谢的影响，该模型保留了真皮结缔组织的正常三维结构和表皮角质形成细胞的动态生长和分层。用H-3-氨基葡萄糖和H-3-胸腺嘧啶核苷标记分别测定透明质酸、蛋白多糖和DNA的合成。利用生物素化的聚集素-连接蛋白复合体研究了透明质酸的总含量和组织分布。在CHASE实验中，低浓度HC(10(-9)M)刺激H-3-氨基葡萄糖掺入表皮透明质酸23%，并使透明质酸消失率降低25%，使培养5天的总透明质酸(单位表皮干重)增加74%。另一方面，高浓度的HC(10(-5)M)在24小时的标记和追逐过程中减少了表皮透明质酸的合成(-42%)和降解(-46%)。5天治疗的累积效果是表皮总透明质酸减少了24%。高剂量(10(-5)M)还可降低角质形成细胞DNA合成和表皮厚度。在真皮中，只有高浓度(10(-5)M)的HC才有效，可将H-3-氨基葡萄糖掺入透明质酸的能力抑制28%。对皮肤组织中透明质酸总含量及消失率无明显影响。所有浓度的HC对表皮和真皮组织中新合成的PGs没有显著影响，但减少了标记的PGs扩散到培养基中。低生理浓度的HC维持了表皮组织中透明质酸的合成活性和高浓度，而高药理剂量的HC则减缓了透明质酸的周转，减少了其在表皮中的含量，这一作用与促进终末分化、降低增殖速度和减少重要角质形成细胞层的数量有关。(C)1995年Wiley-Liss公司
We studied the influence of hydrocortisone (HC) on hyaluronan (HA) metabolism in explants of human skin, a model retaining normal three-dimensional architecture of dermal connective tissue and dynamic growth and stratification of epidermal keratinocytes. The synthesis of hyaluronan and proteoglycans (PGs), and DNA, were determined with H-3-glucosamine and H-3-thymidine labelings, respectively. The total content and histological distribution of hyaluronan was studied utilizing a biotinylated aggrecan-link protein complex. A low concentration of HC (10(-9) M) stimulated the incorporation of H-3-glucosamine into hyaluronan in epidermis by 23% and reduced the disappearance rate of hyaluronan by 25% in chase experiments, resulting in a 74% increase in total hyaluronan (per epidermal dry weight) after a 5-day culture in 10(-9) M HC. On the other hand, a high concentration of HC (10(-5) M) reduced both synthesis (-42%) and degradation (-46%) of epidermal hyaluronan during 24 h labeling and chase periods. The cumulative effect of a 5-day treatment was a 24% decrease of total epidermal hyaluronan. The high dose (10(-5) M) also reduced keratinocyte DNA synthesis and epidermal thickness. In dermis, only the high (10(-5) M) concentration of HC was effective, inhibiting the incorporation of H-3-glucosamine into hyaluronan by 28%. No significant influences on total hyaluronan content or the disappearance rate of hyaluronan in dermal tissue was found. All HC concentrations lacked significant effects on newly synthesized PGs in epidermal and dermal tissues, but reduced the labeled PGs diffusing into culture medium. A low physiological concentration of HC thus maintains active synthesis and high concentration of hyaluronan in epidermal tissue, while high pharmacological doses of HC slows hyaluronan turnover and reduces its content in epidermis, an effect correlated with enhanced terminal differentiation, reduced proliferation rate and reduced number of vital keratinocyte layers. (C) 1995 Wiley-Liss, Inc.