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MicroRNAs: novel regulators involved in the pathogenesis of psoriasis?
Enikö Sonkoly1, Tianling Wei, Peter C J Janson
1Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
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.
Insights
Psoriasis skin shows a unique microRNA expression profile, including elevated miR-203. This suggests microRNAs play a key role in regulating inflammatory skin diseases like psoriasis.
Area of Science:
- Molecular Biology
- Dermatology
- Genetics
Background:
- MicroRNAs (miRNAs) are key gene expression regulators with roles in health and disease.
- Psoriasis is a common chronic inflammatory skin disease significantly impacting patient quality of life.
Purpose of the Study:
- To investigate the specific microRNA expression profile in psoriasis-affected skin.
- To compare miRNA profiles between psoriasis, atopic eczema, and healthy skin.
- To identify specific miRNAs involved in psoriasis pathogenesis.
Main Methods:
- Comparative analysis of microRNA expression in human skin samples (psoriasis, atopic eczema, healthy).
- Identification and characterization of specific microRNAs, including miR-203, in different human tissues and cell types.
- Analysis of the relationship between miR-203 and its target gene, suppressor of cytokine signaling 3 (SOCS-3).
Main Results:
- Psoriasis-affected skin exhibits a distinct microRNA expression profile compared to healthy skin and atopic eczema.
- Leukocyte-derived miRNAs and the keratinocyte-derived miR-203 were identified as psoriasis-specific.
- miR-203 is highly skin-specific, exclusively expressed in keratinocytes, and its upregulation in psoriasis correlates with SOCS-3 downregulation.
Conclusions:
- MicroRNA deregulation is implicated in the pathogenesis of psoriasis.
- miR-203 and its target SOCS-3 pathway may contribute to the inflammatory processes and cellular dysfunction in psoriasis.
- These findings reveal a novel regulatory mechanism in chronic inflammatory skin diseases.
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