Dermal fibroblast expression of stromal cell-derived factor-1 (SDF-1) promotes epidermal keratinocyte proliferation in normal and diseased skin.
Dermal fibroblast expression of stromal cell-derived factor-1 (SDF-1) promotes epidermal keratinocyte proliferation in normal and diseased skin.
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DOI：
10.1007/s13238-015-0198-5
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发表时间：
2015-12
期刊：
影响因子：
21.1
通讯作者：
Quan T
中科院分区：
文献类型：
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作者：
Quan C;Cho MK;Shao Y;Mianecki LE;Liao E;Perry D;Quan T
基质细胞为上皮细胞提供了至关重要的微环境。在这里，我们研究了基质细胞特异性蛋白基质细胞衍生因子 1 (SDF-1) 在正常人类皮肤和患病皮肤组织中的表达和功能。免疫组织学和激光捕获显微切割 (LCM) 联合定量实时 RT-PCR 显示，SDF-1 在体内正常人皮肤的真皮基质细胞中组成型且主要表达。令我们惊讶的是，在体内正常人体皮肤的真皮中观察到极高水平的 SDF-1 转录，其 mRNA 表达水平远高于 I 型胶原（人体皮肤中最丰富和高表达的蛋白质）。 SDF-1 在许多人类皮肤病的组织中也表达上调，包括牛皮癣、基底细胞癌 (BCC) 和鳞状细胞癌 (SCC)。 SDF-1 和 HSP47（热休克蛋白 47）（成纤维细胞标记物）的双重免疫染色显示，成纤维细胞是正常和患病皮肤中基质细胞衍生的 SDF-1 的主要来源。在功能上，SDF-1 激活 ERK（细胞外信号调节激酶）通路并作为有丝分裂原刺激表皮角质形成细胞增殖。真皮成纤维细胞中 SDF-1 的过度表达以及用 rhSDF-1 对皮肤等效培养物进行处理均显着增加了角质形成细胞层的数量和表皮厚度。相反，通过干扰CXCR4（SDF-1的特异性受体）或敲低成纤维细胞中的SDF-1，SDF-1对角质形成细胞增殖的刺激功能几乎完全消除。我们的数据表明，极高水平的 SDF-1 为生理和病理皮肤状况下的表皮角质形成细胞增殖提供了至关重要的微环境。本文的在线版本 (doi:10.1007/s13238-015-0198-5) 包含补充材料，可供授权用户使用。
Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled quantitative real-time RT-PCR revealed that SDF-1 is constitutively and predominantly expressed in dermal stromal cells in normal human skin in vivo. To our surprise, an extremely high level of SDF-1 transcription was observed in the dermis of normal human skin in vivo, evidenced by much higher mRNA expression level than type I collagen, the most abundant and highly expressed protein in human skin. SDF-1 was also upregulated in the tissues of many human skin disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein 47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1 activates the ERK (extracellular-signal-regulated kinases) pathway and functions as a mitogen to stimulate epidermal keratinocyte proliferation. Both overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the skin equivalent cultures significantly increased the number of keratinocyte layers and epidermal thickness. Conversely, the stimulative function of SDF-1 on keratinocyte proliferation was nearly completely eliminated by interfering with CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts. Our data reveal that extremely high levels of SDF-1 provide a crucial microenvironment for epidermal keratinocyte proliferation in both physiologic and pathologic skin conditions. The online version of this article (doi:10.1007/s13238-015-0198-5) contains supplementary material, which is available to authorized users.