生物谷：來自瑞典醫(yī)科大學(xué)Karolinska研究所的科研小組最近首次證明,，一種小型RNA分子——microRNA或許在很多皮膚疾病的發(fā)生過程中起到了關(guān)鍵作用，包括牛皮癬,、過敏性濕疹等,。此項(xiàng)研究發(fā)表在最近新的PLoS ONE期刊上，研究小組由瑞典該領(lǐng)域最著名的學(xué)者M(jìn)ona Stahle教授領(lǐng)導(dǎo),。
microRNA是負(fù)責(zé)調(diào)控基因表達(dá)的RNA分子,，而通過作用于皮膚以及免疫細(xì)胞的不同蛋白和不同細(xì)胞學(xué)機(jī)制，這些小型的RNA分子或許是皮膚病發(fā)生過程的關(guān)鍵因素,。因此基于microRNA的治療手段未來可能成為比目前針對(duì)單個(gè)蛋白方法更有效的治療方案,。
Andor Pivarcsi和Eniko Sonkoly共同指導(dǎo)研究進(jìn)行，Pivarcsi表示：“我們相信microRNA同樣在很多其它的常見慢性炎癥疾病中起著重要的調(diào)控作用,，例如關(guān)節(jié)炎和某些自體免疫疾病等,。”
研究結(jié)果顯示，在患有牛皮癬的患者體內(nèi),，其microRNA分子的表達(dá)方式和正常人的并不一樣,，除此之外，這些患者的microRNA表達(dá)和過敏性濕疹患者的也不相同,。其中的一個(gè)分子miR-203引起了科學(xué)家們特別的關(guān)注,，因?yàn)樵摲肿釉谂Ｆぐ_發(fā)生過程中大大的被激發(fā)，并且只在皮膚的上皮細(xì)胞和角質(zhì)化細(xì)胞中得到表達(dá),。
在這以前,，沒有人研究過這類最近才被發(fā)現(xiàn)的小分子是否對(duì)于炎癥類疾病的發(fā)生起到了重要的作用。牛皮癬和過敏性濕疹是最常見的慢性皮膚炎癥類疾病,。盡管科學(xué)家們已經(jīng)在這方面進(jìn)行了大量的研究,，但是目前還尚不清楚影響這些疾病的內(nèi)在機(jī)制，這無疑妨礙了相關(guān)藥物的研制,。 （教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news103382317.html
原始出處:
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
