eISSN: 2299-0046
ISSN: 1642-395X
Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii
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SCImago Journal & Country Rank
2/2021
vol. 38
 
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abstract:
Original paper

Differences in expression of genes related to drug resistance and miRNAs regulating their expression in skin fibroblasts exposed to adalimumab and cyclosporine A

Beniamin Grabarek
1, 2, 3
,
Piotr Schweizer
1
,
Iwona Adwent
1
,
Dominika Wcisło-Dziadecka
4
,
Jakub Krzaczyński
3
,
Celina Kruszniewska-Rajs
3
,
Joanna Gola
3

  1. Katowice School of Technology, The University of Science and Art, Katowice, Poland
  2. Centre of Oncology, M. Sklodowska-Curie Memorial Institute, Cracow Branch, Poland
  3. Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland
  4. Department of Cosmetology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland
Adv Dermatol Allergol 2021; XXXVIII (2): 249-255
Online publish date: 2020/01/09
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Introduction
Adalimumab and cyclosporine A are drugs used in moderate to severe forms of psoriasis. Despite the molecular orientation of the drugs, there is a loss of adequate cell sensitivity to the anti-cytokine therapy.

Aim
To determine the changes in the gene expression profile associated with drug resistance in the culture of normal human dermal fibroblasts (NHDF) exposed to adalimumab or cyclosporine A compared to the controls.

Material and methods
NHDF was exposed to adalimumab/cyclosporine A for 2, 8, 24 h compared to the control culture. Molecular analysis was performed using mRNA and miRNA microarray techniques. The obtained results were analysed using PL – Grid infrastructure (p < 0.05).

Results
Of the 22277 ID mRNA, 47 are associated with drug resistance, of which the change in expression of 17 mRNA ID is statistically significant (p < 0.05). The greatest change in transcriptional activity (FC ≥ 1.3) was observed for GLO1, SLC10A3, TUFT1, STATH, ABCB1, AGTR1. Expression of these genes can be regulated by miR-199a-5p, miR-1231, miR-34a, miR-3188, and miR-106a (except AGTR1).

Conclusions
The analysis of changes in the expression of mRNA and miRNA related to drug resistance gives the possibility of monitoring the effectiveness of anti-cytokine therapy.

keywords:

psoriasis, drug resistance, personalized therapy, miRNA

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