Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark.
J Dermatol Sci. 2010 Jun;58(3):177-85. doi: 10.1016/j.jdermsci.2010.03.004. Epub 2010 Mar 17.
Psoriasis is a chronic inflammatory skin disease often seen in patients with a genetic susceptibility. MicroRNAs (miRNA) are endogenous, short RNA molecules that can bind to parts of mRNA target genes, thus inhibiting their translation and causing accelerated turnover or transcript degradation. MicroRNAs are important in the pathogenesis of human diseases such as immunological disorders, as they regulate a broad range of biological processes.
We investigated miRNA-mRNA interactions in involved (PP) and non-involved (PN) psoriatic skin compared with healthy skin (NN).
Biopsies were obtained from PP, PN and NN, the miRNA and mRNA expression was analyzed by microarray techniques and a subset of miRNAs and mRNAs were validated by q-RT-PCR. Novel target interactions in psoriasis were found using PubMed, miRBase and RNAhybrid. In addition, TIMP3 protein expression was studied in PP, PN and NN. Finally, the miR-221/2-TIMP3 target interaction was studied in primary human keratinocytes by endogenous overexpression of the miRNAs.
We identified 42 upregulated miRNAs and 5 downregulated miRNAs in PP compared with NN, and only few deregulated miRNAs in PN compared with NN. Based on the miRNA and mRNA profiles miR-21, -205, -221 and -222 were found to have the following potential mRNA targets in psoriatic skin: PDCD4, TPM1, P57, C-KIT, RTN4, SHIP2, TIMP3, RECK and NFIB. The identified target mRNAs were likely to be involved in cellular growth, proliferation, apoptosis and degradation of the extracellular matrix. Finally we found that TIMP3 is downregulated in psoriatic skin. In vitro overexpression of miR-221 and miR-222 lead to degradation of TIMP3 resulting in decreased TIMP3 protein level.
Our data indicate several novel important associations for miRNAs in psoriasis and in particular the miR-221/2-TIMP3 target interaction could among others play a role in the psoriasis pathogenesis.
银屑病是一种常见于遗传易感性患者的慢性炎症性皮肤病。microRNAs (miRNA) 是内源性的短 RNA 分子，可以与 mRNA 靶基因的部分结合，从而抑制其翻译并导致加速周转或转录降解。miRNA 在免疫紊乱等人类疾病的发病机制中非常重要，因为它们调节广泛的生物过程。
我们研究了与健康皮肤（NN）相比，受累（PP）和非受累（PN）银屑病皮肤中的 miRNA-mRNA 相互作用。
从 PP、PN 和 NN 中获取活检，通过微阵列技术分析 miRNA 和 mRNA 表达，通过 q-RT-PCR 验证 miRNA 和 mRNA 的亚组。使用 PubMed、miRBase 和 RNAhybrid 寻找银屑病中的新型靶相互作用。此外，还研究了 PP、PN 和 NN 中 TIMP3 蛋白的表达。最后，通过内源性过表达 miRNA 研究了原发性人角质形成细胞中 miR-221/2-TIMP3 靶相互作用。
与 NN 相比，我们在 PP 中发现了 42 个上调的 miRNA 和 5 个下调的 miRNA，而在 PN 中与 NN 相比，只有少数 miRNA 失调。根据 miRNA 和 mRNA 谱，发现 miR-21、-205、-221 和 -222 在银屑病皮肤中具有以下潜在的 mRNA 靶标：PDCD4、TPM1、P57、C-KIT、RTN4、SHIP2、TIMP3、RECK 和 NFIB。鉴定的靶 mRNA 可能参与细胞生长、增殖、凋亡和细胞外基质降解。最后，我们发现 TIMP3 在银屑病皮肤中下调。体外过表达 miR-221 和 miR-222 导致 TIMP3 降解，从而降低 TIMP3 蛋白水平。
我们的数据表明 miRNA 在银屑病中存在几种新的重要关联，特别是 miR-221/2-TIMP3 靶相互作用可能在银屑病发病机制中发挥作用。
