Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2007 Jul 11;2(7):e610. doi: 10.1371/journal.pone.0000610.
MicroRNAs are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in health and disease. Psoriasis is the most prevalent chronic inflammatory skin disease in adults, with a substantial negative impact on the patients' quality of life. Here we show for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema. Among the psoriasis-specific microRNAs, we identified leukocyte-derived microRNAs and one keratinocyte-derived microRNA, miR-203. In a panel of 21 different human organs and tissues, miR-203 showed a highly skin-specific expression profile. Among the cellular constituents of the skin, it was exclusively expressed by keratinocytes. The up-regulation of miR-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of miR-203, suppressor of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions. Our results suggest that microRNA deregulation is involved in the pathogenesis of psoriasis and contributes to the dysfunction of the cross talk between resident and infiltrating cells. Taken together, a new layer of regulatory mechanisms is involved in the pathogenesis of chronic inflammatory skin diseases.
微小 RNA 是一类新发现的基因表达转录后调控因子,在健康和疾病中具有关键作用。银屑病是成人中最常见的慢性炎症性皮肤病,对患者的生活质量有重大负面影响。在这里,我们首次表明,与健康皮肤或另一种慢性炎症性皮肤病特应性皮炎相比,银屑病皮肤具有特定的 microRNA 表达谱。在银屑病特异性 microRNA 中,我们鉴定了白细胞衍生的 microRNA 和一种角质形成细胞衍生的 microRNA,miR-203。在 21 种不同的人类器官和组织的面板中,miR-203 表现出高度的皮肤特异性表达谱。在皮肤的细胞成分中,它仅由角质形成细胞表达。miR-203 在银屑病斑块中的上调与 miR-203 的一个进化保守靶标,细胞因子信号转导抑制因子 3(SOCS-3)的下调同时发生,SOCS-3 参与炎症反应和角质形成细胞功能。我们的研究结果表明,microRNA 失调参与了银屑病的发病机制,并导致驻留细胞和浸润细胞之间的相互作用失调。总之,在慢性炎症性皮肤病的发病机制中涉及到一个新的调控机制层。