Abstract

miRNAs have been associated with psoriasis since just over a decade. However, we are far from a complete understanding of their role during the development of this disease. Our objective was to characterize the cutaneous expression of miRNAs not previously described in psoriasis, the changes induced following the treatment with biologicals and their association with disease improvement. Next generation sequencing was performed from five skin samples from psoriasis patients (lesional and non-lesional skin) and five controls, and from this cohort, 12 microRNAs were selected to be analyzed in skin samples from 44 patients with plaque psoriasis. In 15 patients, an additional sample was obtained after three months of biological treatment. MiR-9-5p, miR-133a-3p and miR-375 were downregulated in the lesional skin of psoriasis patients. After treatment, expression of miR-133a-3p, miR-375, miR-378a and miR-135b in residual lesions returned towards the levels observed in non-lesional skin. The decrease in miR-135b levels after treatment with biologics was associated with both the improvement of patients evaluated through Psoriasis Area and Severity Index score and the decrease in local inflammatory response. Moreover, basal expression of miR-135b along with age was associated with the improvement of psoriasis, suggesting its possible usefulness as a prognostic biomarker.

Highlights

  • Psoriasis is a very complex disease that results from the interplay between the immune system, epidermal cells, genetic and environmental factors

  • To analyze the relation between miRNA expression in lesional or non-lesional skin and psoriasis severity, we identified the clinical and demographic variables associated with PASI

  • EV-associated miRNAs signature increased in serum of psoriasis patients that returns

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Summary

Introduction

Psoriasis is a very complex disease that results from the interplay between the immune system, epidermal cells, genetic and environmental factors. Our knowledge about many biological functions of miRNAs comes from studies of overexpression or blockade of individual miRNAs. studies from knockout animals have shown that the absence of a single miRNA results in modest or no clear alteration of phenotype, supporting the notion that miRNAs do not work in isolation, but as part of regulatory networks of gene expression [3,4,5]. An additional feature of miRNAs that adds complexity to their function is that one single miRNA is able to regulate the expression of many genes, each of them being a possible target of many miRNAs [6]

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