MicroRNAs: Novel Regulators Involved in the Pathogenesis of Psoriasis?

被引:620
作者
Sonkoly, Eniko [1 ]
Wei, Tianling [1 ]
Janson, Peter C. J. [2 ]
Saaf, Annika [3 ]
Lundeberg, Lena [1 ]
Tengvall-Linder, Maria [2 ]
Norstedt, Gunnar [3 ]
Alenius, Harri [4 ]
Homey, Bernhard [5 ]
Scheynius, Annika [2 ]
Stahle, Mona [1 ]
Pivarcsi, Andor [1 ]
机构
[1] Karolinska Inst, Dept Med, Dermatol & Venereol Unit, Stockholm, Sweden
[2] Karolinska Inst, Dept Med, Clin Allergy Res Unit, Stockholm, Sweden
[3] Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden
[4] Finnish Inst Occupat Hlth, Unit Excellence Immunotoxicol, Helsinki, Finland
[5] Univ Dusseldorf, Dept Dermatol, D-4000 Dusseldorf, Germany
来源
PLOS ONE | 2007年 / 2卷 / 07期
基金
英国医学研究理事会;
关键词
D O I
10.1371/journal.pone.0000610
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:8
相关论文
共 22 条
[1]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   Proteome analysis of skin distinguishes acute guttate from chronic plaque psoriasis [J].
Carlén, LM ;
Sánchez, F ;
Bergman, AC ;
Becker, S ;
Hirschberg, D ;
Franzén, B ;
Coffey, J ;
Jörnvall, H ;
Auer, G ;
Alaiya, AA ;
Ståhle, M .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 124 (01) :63-69
[4]   miRNAs, cancer, and stem cell division [J].
Croce, CM ;
Calin, GA .
CELL, 2005, 122 (01) :6-7
[5]   SOCS3 negatively regulates IL-6 signaling in vivo [J].
Croker, BA ;
Krebs, DL ;
Zhang, JG ;
Wormald, S ;
Willson, TA ;
Stanley, EG ;
Robb, L ;
Greenhalgh, CJ ;
Förster, I ;
Clausen, BE ;
Nicola, NA ;
Metcalf, D ;
Hilton, DJ ;
Roberts, AW ;
Alexander, WS .
NATURE IMMUNOLOGY, 2003, 4 (06) :540-545
[6]   MicroRNAs as therapeutic targets [J].
Czech, MP .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (11) :1194-1195
[7]   Increased oxidative damage to fibroblasts in skin with and without lesions in psoriasis [J].
Dimon-Gadal, S ;
Gerbaud, P ;
Thérond, P ;
Guibourdenche, J ;
Anderson, WB ;
Evain-Brion, D ;
Raynaud, F .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 114 (05) :984-989
[8]   Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion [J].
Fischer, Marie ;
Harvima, Ilkka T. ;
Carvalho, Ricardo F. S. ;
Moller, Christine ;
Naukkarinen, Anita ;
Enblad, Gunilla ;
Nilsson, Gunnar .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (10) :2748-2756
[9]   The suppressor of cytokine signaling-3 is upregulated in impaired skin repair:: Implications for keratinocyte proliferation [J].
Goren, Itamar ;
Linke, Andreas ;
Mueller, Elke ;
Pfeilschifter, Josef ;
Frank, Stefan .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (02) :477-485
[10]   Cutting edge:: The orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC) [J].
Homey, B ;
Wang, W ;
Soto, H ;
Buchanan, ME ;
Wiesenborn, A ;
Catron, D ;
Müller, A ;
McClanahan, TK ;
Dieu-Nosjean, MC ;
Orozco, R ;
Ruzicka, T ;
Lehmann, P ;
Oldham, E ;
Zlotnik, A .
JOURNAL OF IMMUNOLOGY, 2000, 164 (07) :3465-3470