The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions

Arch Dermatol Res. 2017 Sep;309(7):557-565. doi: 10.1007/s00403-017-1752-1. Epub 2017 Jun 20.

Abstract

Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

Keywords: Chronic inflammation; Hidradenitis suppurativa; Inflammation; Inflammatory skin disease; RNA-induced silencing complex; microRNA.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Argonaute Proteins / biosynthesis
  • Cell Adhesion Molecules / biosynthesis
  • Endonucleases
  • Eukaryotic Initiation Factors / biosynthesis
  • Female
  • Hidradenitis Suppurativa / genetics*
  • Hidradenitis Suppurativa / pathology*
  • Humans
  • Inflammation / pathology
  • Male
  • Membrane Proteins
  • MicroRNAs / genetics*
  • Middle Aged
  • Nuclear Proteins / biosynthesis
  • Prospective Studies
  • RNA-Binding Proteins / biosynthesis
  • RNA-Induced Silencing Complex / genetics*
  • Skin / pathology*

Substances

  • AGO1 protein, human
  • AGO2 protein, human
  • Argonaute Proteins
  • Cell Adhesion Molecules
  • Eukaryotic Initiation Factors
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • Nuclear Proteins
  • PRKRA protein, human
  • RNA-Binding Proteins
  • RNA-Induced Silencing Complex
  • trans-activation responsive RNA-binding protein
  • Endonucleases
  • SND1 protein, human