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MicroRNAs and potential target interactions in psoriasis.
- Source :
-
Journal of dermatological science [J Dermatol Sci] 2010 Jun; Vol. 58 (3), pp. 177-85. Date of Electronic Publication: 2010 Mar 17. - Publication Year :
- 2010
-
Abstract
- Background: Psoriasis is a chronic inflammatory skin disease often seen in patients with a genetic susceptibility. MicroRNAs (miRNA) are endogenous, short RNA molecules that can bind to parts of mRNA target genes, thus inhibiting their translation and causing accelerated turnover or transcript degradation. MicroRNAs are important in the pathogenesis of human diseases such as immunological disorders, as they regulate a broad range of biological processes.<br />Objective: We investigated miRNA-mRNA interactions in involved (PP) and non-involved (PN) psoriatic skin compared with healthy skin (NN).<br />Methods: Biopsies were obtained from PP, PN and NN, the miRNA and mRNA expression was analyzed by microarray techniques and a subset of miRNAs and mRNAs were validated by q-RT-PCR. Novel target interactions in psoriasis were found using PubMed, miRBase and RNAhybrid. In addition, TIMP3 protein expression was studied in PP, PN and NN. Finally, the miR-221/2-TIMP3 target interaction was studied in primary human keratinocytes by endogenous overexpression of the miRNAs.<br />Results: We identified 42 upregulated miRNAs and 5 downregulated miRNAs in PP compared with NN, and only few deregulated miRNAs in PN compared with NN. Based on the miRNA and mRNA profiles miR-21, -205, -221 and -222 were found to have the following potential mRNA targets in psoriatic skin: PDCD4, TPM1, P57, C-KIT, RTN4, SHIP2, TIMP3, RECK and NFIB. The identified target mRNAs were likely to be involved in cellular growth, proliferation, apoptosis and degradation of the extracellular matrix. Finally we found that TIMP3 is downregulated in psoriatic skin. In vitro overexpression of miR-221 and miR-222 lead to degradation of TIMP3 resulting in decreased TIMP3 protein level.<br />Conclusion: Our data indicate several novel important associations for miRNAs in psoriasis and in particular the miR-221/2-TIMP3 target interaction could among others play a role in the psoriasis pathogenesis.<br /> (Copyright 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Adult
Apoptosis genetics
Biopsy
Cells, Cultured
Female
Gene Expression Profiling
Humans
Keratinocytes cytology
Male
MicroRNAs genetics
Middle Aged
Oligonucleotide Array Sequence Analysis
Psoriasis etiology
RNA, Messenger metabolism
Transcriptional Activation physiology
Young Adult
Keratinocytes physiology
MicroRNAs metabolism
Psoriasis genetics
Psoriasis metabolism
Tissue Inhibitor of Metalloproteinase-3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-569X
- Volume :
- 58
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of dermatological science
- Publication Type :
- Academic Journal
- Accession number :
- 20417062
- Full Text :
- https://doi.org/10.1016/j.jdermsci.2010.03.004