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Changes in the Expression Profile of JAK/STAT Signaling Pathway Genes and Mirnas Regulating their Expression Under

Beniamin Grabarek1, Dominika Wcislo-Dziadecka2, Joanna Gola1

  • 1Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, ul. Jedności 8, 41-206 Sosnowiec, Poland.

Current Pharmaceutical Biotechnology
|July 31, 2018
PubMed
Abstract

Insights

Adalimumab influences the JAK/STAT pathway in skin cells, with microRNAs (miRNAs) regulating gene expression. Changes in mRNA and miRNA profiles may serve as markers for treatment effectiveness.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Adalimumab is a biologic therapy targeting inflammatory pathways.
  • The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is crucial in cellular signaling and immune responses.
  • Understanding adalimumab's molecular effects on skin cells is vital for optimizing treatment.

Purpose of the Study:

  • To investigate adalimumab's impact on JAK/STAT signaling gene expression in Normal Human Dermal Fibroblast (NHDF) cells.
  • To identify microRNAs (miRNAs) that regulate these JAK/STAT pathway genes.
  • To explore potential molecular markers for adalimumab treatment efficacy.

Main Methods:

  • NHDF cells were cultured with or without adalimumab for 2, 8, and 24 hours.
  • Microarray technology was employed to analyze messenger RNA (mRNA) and miRNA expression profiles.
  • Bioinformatic analysis identified differentially expressed genes and miRNAs.

Main Results:

  • Out of 22,283 identified mRNAs, 37 were associated with the JAK/STAT pathway, with 18 showing differential expression upon adalimumab treatment.
  • Analysis of 1,105 identified miRNAs revealed 20 differentiating miRNAs at 2 hours, 9 at 8 hours, and 3 at 24 hours post-treatment.
  • A significant role for miRNAs in regulating JAK/STAT pathway gene expression was observed.

Conclusions:

  • MicroRNAs play a critical role in regulating genes within the JAK/STAT signaling pathway.
  • Changes in mRNA and miRNA expression profiles in NHDF cells can serve as complementary molecular markers for adalimumab treatment effectiveness.
  • This study provides insights into the molecular mechanisms of adalimumab action in dermal fibroblasts.
Keywords:
JAK/STAT signaling pathwayNHDF culturesadalimumabinterleukinloss of sensitivity to treatmentmicro RNA.

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