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.
Highlights
MicroRNAs are,22 nt noncoding RNAs that can suppress the expression of protein-coding genes by targeting cognate messenger RNAs for translational repression or, less frequently, degradation [1,2]
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
To determine whether miRNAs are involved in the pathogenesis of psoriasis, we performed a comprehensive analysis of all human miRNAs registered in mirBase 8.0 (342 known human miRNAs) in skin lesions of patients with psoriasis (n = 3) and compared it to healthy human skin (n = 4) or to lesional skin from patients with a nonpsoriatic chronic inflammatory skin disease, atopic eczema (n = 3)
Summary
MicroRNAs (miRNAs) are ,22 nt noncoding RNAs that can suppress the expression of protein-coding genes by targeting cognate messenger RNAs for translational repression or, less frequently, degradation [1,2]. We demonstrate that psoriasis is characterized by a specific miRNA expression profile that differs from that of healthy skin or another chronic inflammatory disease, atopic eczema. These results suggest that miRNAs contribute to psoriasis pathogenesis by modulating protein expression and cellular functions in both keratinocytes and infiltrating immune cells.
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