生物谷：来自瑞典医科大学Karolinska研究所的科研小组最近首次证明，一种小型RNA分子——microRNA或许在很多皮肤疾病的发生过程中起到了关键作用，包括牛皮癣、过敏性湿疹等。此项研究发表在最近新的PLoS ONE期刊上，研究小组由瑞典该领域最著名的学者Mona Stahle教授领导。
microRNA是负责调控基因表达的RNA分子，而通过作用于皮肤以及免疫细胞的不同蛋白和不同细胞学机制，这些小型的RNA分子或许是皮肤病发生过程的关键因素。因此基于microRNA的治疗手段未来可能成为比目前针对单个蛋白方法更有效的治疗方案。
Andor Pivarcsi和Eniko Sonkoly共同指导研究进行，Pivarcsi表示：“我们相信microRNA同样在很多其它的常见慢性炎症疾病中起着重要的调控作用，例如关节炎和某些自体免疫疾病等。”
研究结果显示，在患有牛皮癣的患者体内，其microRNA分子的表达方式和正常人的并不一样，除此之外，这些患者的microRNA表达和过敏性湿疹患者的也不相同。其中的一个分子miR-203引起了科学家们特别的关注，因为该分子在牛皮癣发生过程中大大的被激发，并且只在皮肤的上皮细胞和角质化细胞中得到表达。
在这以前，没有人研究过这类最近才被发现的小分子是否对于炎症类疾病的发生起到了重要的作用。牛皮癣和过敏性湿疹是最常见的慢性皮肤炎症类疾病。尽管科学家们已经在这方面进行了大量的研究，但是目前还尚不清楚影响这些疾病的内在机制，这无疑妨碍了相关药物的研制。 （教育部科技发展中心）
原文链接：http://www.physorg.com/news103382317.html
原始出处:
PLoS ONE
Received: May 21, 2007; Accepted: June 13, 2007; Published: July 11, 2007
MicroRNAs: Novel Regulators Involved in the Pathogenesis of Psoriasis?
Enikö Sonkoly1*, Tianling Wei1, Peter C.J. Janson2, Annika Sääf3, Lena Lundeberg1, Maria Tengvall-Linder2, Gunnar Norstedt3, Harri Alenius4, Bernhard Homey5, Annika Scheynius2, Mona Ståhle1, Andor Pivarcsi1*
1 Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 2 Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 3 Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden, 4 Unit of Excellence in Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland, 5 Department of Dermatology, Heinrich-Heine University, Düsseldorf, Germany
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.
Figure 1. MicroRNA expression profiling in psoriasis, atopic eczema and healthy skin.
(A) microRNA (miRNA) array comparison of skin from healthy individuals (H, n = 4) and lesional skin from patients with psoriasis (PSO, n = 3) and atopic eczema (AE, n = 3). Total RNA from skin biopsies was labeled and hybridized to microarrays containing probes corresponding to known miRNA sequences. The heat map summarizes the biological replicates for the skin specimens, and four technical replicates for each set. Color intensity is scaled within each row so that the highest expression value corresponds to bright red and the lowest to bright green. Gene names are listed to the right. (B) miRNAs showing more than 1.7-fold change between psoriasis and healthy skin (left) and atopic eczema and healthy skin (right) according to the SAM algorithm. miRNAs that are over-expressed in both psoriasis and in atopic eczema are highlighted in yellow, miRNAs that are down-regulated in both diseases are highlighted in blue. (C) The expressions of the functionally active, mature forms of four miRNAs were analyzed using quantitative real-time PCR in the skin of 26 healthy individuals, and lesional skin samples of 20 patients with atopic eczema and 25 patients with psoriasis. The results for individual patients and mean are shown. Data are expressed in relative units compared to U48 RNA. ***p<0.001, **p<0.01.
doi:10.1371/journal.pone.0000610.g001
