Propionibacterium acnes Activates the IGF-1/IGF-1R System in the Epidermis and Induces Keratinocyte Proliferation
Propionibacterium acnes Activates the IGF-1/IGF-1R System in the Epidermis and Induces Keratinocyte Proliferation
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DOI：
10.1038/jid.2010.281
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发表时间：
2011-01-01
影响因子：
6.5
通讯作者：
Dreno, Brigitte
中科院分区：
文献类型：
--
作者：
Isard, Olivia;Knol, Anne C.;Dreno, Brigitte
痤疮丙酸杆菌在痤疮皮损的发生中起重要作用。 IGF-1 通过激活 IGF-1 受体 (IGF-1R) 刺激角质细胞增殖。锌已被证明可以有效对抗炎症性痤疮并调节 IGF-1 系统。我们的目标是研究痤疮丙酸杆菌提取物对 IGF-1 和 IGF-1R 表达的调节作用，并确定葡萄糖酸锌对 IGF-1 和 IGF-1R 表达的调节作用。在体内，我们分析了痤疮病变和健康皮肤的活组织检查，在体外，我们使用与两种痤疮丙酸杆菌提取物（膜部分（MF）和胞质蛋白）（含或不含锌）一起孵育的皮肤外植体。使用免疫组织化学评估IGF-1和IGF-1R表达，并通过ELISA测量上清液中IGF-1的产生。然后，使用定量 PCR 对正常人表皮角质形成细胞 (NHEK) 分析 IGF-1 和 IGF-1R mRNA 水平。 IGF-1 和 IGF-1R 在痤疮皮损中过度表达。 MF 增加外植体表皮中 IGF-1 和 IGF-1R 的表达，并与 Ki-67 和聚丝蛋白的过度表达相关。锌具有下调IGF-1和IGF-1R水平的作用。这些观察结果在 NHEK 中 IGF-1R 的 mRNA 水平上得到了证实。这些结果证明痤疮丙酸杆菌可以通过刺激IGF/IGF-1R系统来诱导粉刺的形成。此外，锌会下调该途径。
Propionibacterium acnes has a major role in the development of acne lesions. IGF-1 stimulates the proliferation of keratinocytes via an activation of the IGF-1 receptor (IGF-1R). Zinc has been proven to work efficiently against inflammatory acne and to modulate the IGF-1 system. Our objectives were to study the modulation of IGF-1 and IGF-1R expression by P. acnes extracts and to determine their modulation by zinc gluconate. In vivo, we analyzed biopsies of acne lesions and healthy skin, and in vitro we used skin explants incubated with two P. acnes extracts-membrane fraction (MF) and cytosolic proteins-with or without zinc. IGF-1 and IGF-1R expression was evaluated using immunohistochemistry, and the IGF-1 production in supernatants was measured by ELISA. Then, IGF-1 and IGF-1R mRNA levels were analyzed using quantitative PCR on normal human epidermal keratinocytes (NHEKs). IGF-1 and IGF-1R were overexpressed in acne lesions. MF increased IGF-1 and IGF-1R expression in the epidermis of explants and was associated with an overexpression of both Ki-67 and filaggrin. Zinc had the effect of downregulating IGF-1 and IGF-1R levels. These observations were confirmed at the mRNA level for IGF-1R in NHEKs. These results demonstrate that P. acnes can induce the formation of comedones by stimulating the IGF/IGF-1R system. Moreover, zinc downregulates this pathway.