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首页> 外文期刊>Journal of dermatological science >Modulation of semaphorin 3A expression by calcium concentration and histamine in human keratinocytes and fibroblasts.
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Modulation of semaphorin 3A expression by calcium concentration and histamine in human keratinocytes and fibroblasts.

机译：钙浓度和组胺在人角质形成细胞和成纤维细胞中对信号蛋白3A表达的调节。

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BACKGROUND: Both neurotrophins and chemorepellents are involved in the elongation and sprouting of itch-associated C-fibers in the skin. Nerve growth factor (NGF) and semaphorin 3A (Sema3A) are representatives of these two types of axon-guidance factors, respectively. OBJECTIVE: We investigated the effects of calcium concentration and histamine on the expression of NGF and Sema3A in normal human epidermal keratinocytes (NHEK) and normal human fibroblasts (NHFb). METHODS: NHEK and NHFb were cultured under different calcium concentrations (0.15-0.9 mM) with or without histamine, and the expression of mRNA for NGF and SEMA3A was assessed by real-time PCR analysis. An immunohistochemical study was performed for Sema3A using normal skin and skin cancer specimens. RESULTS: In NHEK, SEMA3A expression was elevated by high calcium concentration and reduced by low calcium condition, while NGF expression was not dependent on calcium. Their expressions were unchanged by calcium in NHFb. Immunohistochemically, keratinocytes in the prickle layer of normal epidermis and squamous cell carcinoma cells were positive for Sema3A, sparing basal cells and suprabasal cells. The addition of histamine to NHEK at 10 mug/ml enhanced SEMA3A expression but depressed NGF expression. In NHFb, however, histamine decreased both NGF and SEMA3A levels. CONCLUSIONS: Sema3A inhibits C-fiber elongation/sprouting in the upper layers of the epidermis, where calcium concentration is high, thereby determining the nerve endings. Histamine reduces Sema3A production by fibroblasts, allowing C-fibers to elongate in the dermis. In contrast, the histamine-augmented keratinocyte production of Sema3A might suppress C-fiber elongation and exaggerated pruritus.
机译：背景：神经营养蛋白和化学驱除剂均与皮肤瘙痒相关的C纤维的伸长和发芽有关。神经生长因子（NGF）和信号量3A（Sema3A）分别代表这两种轴突引导因子。目的：研究钙浓度和组胺对正常人表皮角质形成细胞（NHEK）和正常人成纤维细胞（NHFb）中NGF和Sema3A表达的影响。方法：在有或没有组胺的情况下，在不同钙浓度（0.15-0.9 mM）下培养NHEK和NHFb，并通过实时PCR分析评估NGF和SEMA3A的mRNA表达。使用正常皮肤和皮肤癌标本对Sema3A进行了免疫组织化学研究。结果：在NHEK中，高钙浓度下SEMA3A表达升高，而低钙条件下SEMA3A表达降低，而NGF表达不依赖钙。钙在NHFb中的表达没有改变。免疫组织化学观察，正常表皮和鳞状细胞癌的刺皮层中的角质形成细胞Sema3A阳性，基底细胞和基底上细胞除外。在10杯/毫升的NHEK中添加组胺可增强SEMA3A表达，但会抑制NGF表达。但是，在NHFb中，组胺降低了NGF和SEMA3A的水平。结论：Sema3A抑制表皮上层（钙浓度高）的C纤维伸长/发芽，从而确定神经末梢。组胺减少成纤维细胞产生的Sema3A，从而使C纤维在真皮中伸长。相反，组胺增强的Sema3A角质形成细胞的产生可能会抑制C纤维的伸长和皮肤瘙痒的加剧。

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