Integrated microRNA/mRNA expression profiling of the skin of psoriasis patients.
Analysis
Gene expression
Integrated
Psoriasis
microRNA
Journal
Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
24
02
2019
revised:
04
11
2019
accepted:
05
11
2019
pubmed:
18
12
2019
medline:
15
12
2020
entrez:
18
12
2019
Statut:
ppublish
Résumé
Psoriasis is a chronic inflammatory disease characterized by demarcated, raised, and scaling skin lesions. It often serves as a model for immune-mediated disorders. Gene expression profiling of affected skin has allowed insights into psoriasis pathogenesis. However, the mechanisms leading to specific mRNA expression alterations in psoriasis are barely understood. To perform integrated microRNA-mRNA expression studies of non-lesional, peri-lesional, and lesional skin from psoriasis patients. Cutaneous microRNA and mRNA expression profiles of 14 patients using Nanostring nCounter-technology and RNA sequencing as well as in vitro keratinocyte stimulation and qPCR studies. Only 3.5 % of microRNAs manifested a robust gradual expression trend from non-lesional to paired lesional skin, with 61 % being upregulated and 39 % being downregulated. Relevance of these microRNA regulations was supported by their inverse association with 57 % of the mRNA species found to be regulated during psoriatic lesion development. Many of the involved mRNAs were downregulated and functionally related to keratinocyte metabolism, barrier function, and neuronal signaling, and were already regulated in peri-lesional skin. An integrated correlation analysis revealed a robust interaction for 134 microRNAs/mRNAs pairs. In vitro keratinocyte studies of selected microRNAs/mRNAs revealed regulations of all analyzed microRNAs in a psoriasis-like manner by IL-17A/TNF-α (e.g. hsa-miR-23a-3p), IFN-γ (e.g. hsa-miR-106a-5p/miR-17-5p), or IL-24 (e.g. hsa-miR-203a-3p). Moreover, most of their predicted target mRNAs (e.g. ID4, EPHB2) were respectively altered by the same cytokines. Our study suggests that, during development of psoriatic lesions, defined aspects of psoriasis pathogenesis are regulated by the action of microRNAs.
Sections du résumé
BACKGROUND
BACKGROUND
Psoriasis is a chronic inflammatory disease characterized by demarcated, raised, and scaling skin lesions. It often serves as a model for immune-mediated disorders. Gene expression profiling of affected skin has allowed insights into psoriasis pathogenesis. However, the mechanisms leading to specific mRNA expression alterations in psoriasis are barely understood.
OBJECTIVES
OBJECTIVE
To perform integrated microRNA-mRNA expression studies of non-lesional, peri-lesional, and lesional skin from psoriasis patients.
METHODS
METHODS
Cutaneous microRNA and mRNA expression profiles of 14 patients using Nanostring nCounter-technology and RNA sequencing as well as in vitro keratinocyte stimulation and qPCR studies.
RESULTS
RESULTS
Only 3.5 % of microRNAs manifested a robust gradual expression trend from non-lesional to paired lesional skin, with 61 % being upregulated and 39 % being downregulated. Relevance of these microRNA regulations was supported by their inverse association with 57 % of the mRNA species found to be regulated during psoriatic lesion development. Many of the involved mRNAs were downregulated and functionally related to keratinocyte metabolism, barrier function, and neuronal signaling, and were already regulated in peri-lesional skin. An integrated correlation analysis revealed a robust interaction for 134 microRNAs/mRNAs pairs. In vitro keratinocyte studies of selected microRNAs/mRNAs revealed regulations of all analyzed microRNAs in a psoriasis-like manner by IL-17A/TNF-α (e.g. hsa-miR-23a-3p), IFN-γ (e.g. hsa-miR-106a-5p/miR-17-5p), or IL-24 (e.g. hsa-miR-203a-3p). Moreover, most of their predicted target mRNAs (e.g. ID4, EPHB2) were respectively altered by the same cytokines.
CONCLUSION
CONCLUSIONS
Our study suggests that, during development of psoriatic lesions, defined aspects of psoriasis pathogenesis are regulated by the action of microRNAs.
Identifiants
pubmed: 31843230
pii: S0923-1811(19)30342-1
doi: 10.1016/j.jdermsci.2019.11.003
pii:
doi:
Substances chimiques
MicroRNAs
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9-20Informations de copyright
Copyright © 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.