Abstract
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.
MeSH Terms
Adult
Algorithms
Blotting, Western
Dermatitis, Atopic/genetics,pathology
Fibroblasts/physiology
Gene Expression Profiling
Gene Expression Regulation
Humans
Keratinocytes/physiology
Mast Cells/physiology
MicroRNAs/genetics
Psoriasis/etiology,genetics,psychology
Quality of Life
Reference Values
Skin/physiopathology
Skin Physiological Phenomena
T-Lymphocytes/physiology
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Sonkoly Enikö
Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Wei Tianling
Janson Peter C J
Sääf Annika
Lundeberg Lena
Tengvall-Linder Maria
Norstedt Gunnar
Alenius Harri
Homey Bernhard
Scheynius Annika
Ståhle Mona
Pivarcsi Andor
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